Biomedical subjects

M Pestana

Publications and source records attributed to M Pestana.

At least 19 recordsLinked to original sources

PubMed2006

Body composition assessed by impedance changes very early with declining renal graft function.

BACKGROUND: Kidney transplant (Tx) restores renal filtration, although it does not achieve the function of two native kidneys, and with time it may variably involute back to chronic renal failure. We hypothesized that bioelectrical impedance analysis (BIA) might highlight differences for body compartments among Tx with different filtration rates, and we compared them with healthy controls. METHODS: 38 Tx patients (25 males, 13 females) were studied at 75.9 +/- 37.8 months postsurgery and divided into three groups: good creatinine clearance (CrCl, ml/min/1.73 m2; > 65.0), borderline (35.0 < CrCl < 60.0) and bad (CrCl < 35.0). BIA was assessed three times in a year. Total body water, extracellular water (ECW), intracellular water (ICW), Na:K exchange rate (Nae:Ke) and phase angle were studied. Healthy (n = 11) and hemodialysis (n = 11) groups were also studied. RESULTS: BIA showed no differences between healthy controls and good Tx while both borderline and bad Tx presented a significantly higher ECW and lower ICW than either good Tx or normal controls. Only good CrCl was different from predialysis. CONCLUSIONS: A good kidney graft manages to restore and maintain normal body composition, even with potential disturbances brought about by steroids and cyclosporine. With mild renal dysfunction a change in body compartments was observed, moving towards the composition of that with chronic renal failure patients.

Adult↗

PubMed2005

Blunted renal dopaminergic system activity in HgCl2-induced membranous nephropathy.

The present study evaluated the possible role of the renal dopaminergic system in the sodium retention of HgCl2-induced nephrotic syndrome. The time courses of urinary excretion of sodium, protein, dopamine and the precursor l-3,4-dihydroxyphenylalanine (L-Dopa) were evaluated in HgCl2-treated and control rats up to day 21. The renal aromatic l-amino acid decarboxylase (AADC) activity, the enzyme responsible for the synthesis of renal dopamine, was evaluated during negligible proteinuria accompanied with enhanced sodium retention (day 7), increased proteinuria accompanied with greatest sodium retention (day 14) as well as during increased proteinuria accompanied with negative sodium balance (day 21). Also, the influence of volume expansion (VE, 5% bw) and the effects of the D1-like agonist fenoldopam (10 microg kg bw(-1) min(-1)) on natriuresis and on proximal tubular Na+,K+-ATPase activity were examined on day 14. The daily urinary dopamine output and urinary dopamine/L-Dopa ratios were reduced in HgCl2-treated rats from day 2 and beyond. This was accompanied by a marked decrease in renal AADC throughout the study. During VE, the fenoldopam-induced inhibition of proximal tubular Na+,K+-ATPase activity was similar between HgCl2-treated and control rats. However, the urinary sodium excretion during fenoldopam infusion was markedly increased by 60% to 120% in control rats but was not altered in HgCl2-treated rats. It is concluded that HgCl2 nephrosis is associated with a blunted renal dopaminergic system activity. However, the lack of renal dopamine in HgCl2 nephrosis does not appear to be related with the overall renal sodium retention in a state of proteinuria.

Animals↗

PubMed2005

Jejunal dopamine and Na,K+-ATPase activity in nephrotic syndrome.

BACKGROUND: The occurrence of complementary functions in sodium transport between the intestine and the kidney was suggested to occur when the renal function is immature or compromised and jejunal dopamine has been implicated in this renal-intestinal cross-talk. The jejunal sodium transport was not previously evaluated in the nephrotic syndrome. METHODS: We examined the jejunal Na(+),K(+)-ATPase activity and the role of dopamine in puromycin aminonucleoside (PAN) and HgCl(2)-induced nephrotic syndrome rat models. RESULTS: In both nephrotic syndrome rat models, the jejunal Na(+),K(+)-ATPase activity was reduced during greatest sodium retention and ascites accumulation (PAN nephrosis, day 7; HgCl(2) nephrosis, day 14), whereas during enhanced sodium excretion and ascites mobilization the jejunal Na(+),K(+)-ATPase activity was increased in HgCl(2) nephrosis (day 21) and was similar to controls in PAN nephrosis (day 14). In both PAN- and HgCl(2)-induced nephrosis, the jejunal aromatic L-amino acid decarboxylase (AADC) activity, the enzyme responsible for the synthesis of jejunal dopamine, did not differ from controls. In addition, the jejunal Na(+),K(+)-ATPase activity was not sensitive to inhibition by dopamine (1 microM) in both experimental groups throughout the study. CONCLUSIONS: In the nephrotic syndrome the jejunal Na(+),K(+)-ATPase activity may respond in a compensatory way to changes in extracellular volume, through dopamine-independent mechanisms.

Animals↗

PubMed2005

Salt sensitivity of blood pressure in patients with psoriasis on ciclosporin therapy.

BACKGROUND: Hypertension is one of the main side-effects of long-term therapy with ciclosporin. However, the influence of salt intake on the 24-h mean blood pressure of patients with psoriasis treated with ciclosporin is not known. OBJECTIVES: To evaluate, in patients with psoriasis, the sodium sensitivity of the ciclosporin-induced rise in blood pressure. METHODS: The 24-h ambulatory blood pressure was evaluated in 13 patients with psoriasis (age range 20-57 years) in two phases, before (phase I) and after the completion of 4 months of therapy with ciclosporin 3 mg kg(-1) daily (phase II). In both phases, the patients were studied in conditions of low sodium (LS) intake followed by a high sodium (HS) diet. RESULTS: Twenty-four-hour mean +/- SD blood pressure during LS and HS intake was, respectively, 86.3 +/- 1.6 mmHg and 85.5 +/- 1.8 mmHg during phase I, and 88.5 +/- 1.5 mmHg and 91.8 +/- 2.2 mmHg (P < 0.001 vs. phase I, HS; P < 0.05 vs. phase II, LS) during phase II. The median (interquartile range) sodium sensitivity index was greater during phase II than during phase I: - 0.0028 (- 0.0071 to 0.0009) vs. 0.0065 (- 0.0055 to 0.0258) (P < 0.02). The plasma levels and the daily urinary excretion of noradrenaline did not differ between phases I and II. CONCLUSIONS: The ciclosporin-induced rise in blood pressure is sodium sensitive. It is also suggested that sympathetic activation is not involved in the pathogenesis of ciclosporin-induced rise in blood pressure.

Adult↗

PubMed2004

Renal dopaminergic system activity in the rat remnant kidney.

BACKGROUND: Renal dopamine exerts natriuretic and diuretic effects by activating D1-like receptors. Uninephrectomy results in increased renal dopaminergic activity and dopamine-sensitive enhanced natriuresis. METHODS: The present study evaluated renal adaptations in sodium handling and the role of dopamine in rats submitted to (3/4) nephrectomy: right nephrectomy and excision of both poles of the left kidney ((3/4)nx rats). RESULTS: Two weeks after surgery the absolute urinary levels of dopamine were markedly reduced in (3/4)nx rats whereas the urinary dopamine excretion per % of residual nephrons was significantly increased in the remnant kidney of (3/4)nx rats. The V(max) values for renal aromatic L-amino acid decarboxylase, the enzyme responsible for the synthesis of renal dopamine, were decreased in (3/4)nx rats. Renal catechol-O-methyltransferase activity, the enzyme responsible for the methylation of dopamine, was increased in (3/4)nx rats whereas the renal activities of monoamine oxidases A and B did not differ between (3/4)nx and Sham animals. Volume expansion (5% body weight) resulted in similar natriuretic responses in (3/4)nx and Sham rats. During D1 antagonist administration (Sch-23390, 30 microg x h(-1) x kg(-1)) the natriuretic response to volume expansion was reduced in (3/4)nx rats more pronouncedly than in Sham animals. CONCLUSION: The decrease in absolute renal dopamine output in (3/4)nx rats is related with reduced renal synthesis and enhanced O-methylation of the amine. However, this is accompanied in (3/4)nx rats by increased renal dopamine excretion per residual nephrons and dopamine-sensitive enhanced natriuresis.

Animals↗

PubMed2003

Differences in the renal dopaminergic system activity between Wistar rats from two suppliers.

AIM: Dopamine of renal origin reduces tubular sodium reabsorption and controls blood pressure. The present study evaluated renal dopaminergic activity and its response to uninephrectomy in Wistar Han rats from two suppliers, Harlan (W-H) and Charles River (W-CR). RESULTS: After uninephrectomy, the fractional excretion of sodium (FENa+) increased in both W-CR and W-H rats (W-CR: from 0.17 +/- 0.01 to 0.27 +/- 0.02%; W-H: from 0.39 +/- 0.04 to 0.54 +/- 0.04%, P < 0.05); however, in W-CR rats the FENa+ was lower than in W-H rats in both Sham and uninephrectomized (Unx) animals (P < 0.05). Systolic blood pressure in Unx W-CR rats was higher than in Unx W-H animals (131 +/- 3 vs. 122 +/- 2 mmHg, P < 0.05). Uninephrectomy was accompanied in W-H rats by increases in urinary levels (nmol g kidney(-1) day(-1)) of dopamine (10.3 +/- 0.5 vs. 8.3 +/- 0.7, P < 0.05) and 3,4-dihydroxyphenylacetic acid (DOPAC) (30.5 +/- 3.7 vs. 21.3 +/- 1.4, P < 0.05) and increases (P < 0.05) in maximal velocity values (Vmax in nmol mg prot(-1) 15 min(-1), 325 +/- 12 vs. 265 +/- 3) for renal aromatic L-amino acid decarboxylase (AADC), the enzyme responsible for the synthesis of renal dopamine. By contrast, in W-CR rats uninephrectomy did not change either the urinary levels of dopamine (7.1 +/- 0.5 vs. 7.6 +/- 0.7) and DOPAC (25.0 +/- 1.9 vs. 24.8 +/- 4.1) or AADC activity (Vmax 199 +/- 3 vs. 193 +/- 9). The Vmax values for renal AADC in W-CR rats were lower than those found in corresponding W-H animals. CONCLUSION: Wistar rats from different suppliers represent an important source of variability in the renal dopaminergic system activity. This may contribute to differences in sodium balance and blood pressure control in response to uninephrectomy.

3,4-Dihydroxyphenylacetic Acid↗

PubMed2001

sTNFRI and sTNFRII synthesis by fine-needle aspiration biopsy sample cultures is significantly associated with acute rejection in kidney transplantation.

BACKGROUND: Previously we reported that cultures of fine-needle aspiration biopsy (FNAB) samples synthesize different cytokine pattern depending on the alloimmune response towards the kidney graft. However, we failed to find a clear picture for growth factors implicated in early T-cell activation (interferon-gamma, interleukin [IL]-4, IL-12), although we observed that interleukin-1 receptor antagonist (IL-1ra) was associated with absence of acute rejection. We have now studied tumor necrosis factor-alpha (TNF-alpha) and its two soluble receptors, sTNFRI and sTNFRII, IL-1beta and soluble IL-1 receptor II (sIL-1RII), and leukemia inhibitory factor (LIF), all potential modulators of T-cell activation. METHODS: Sixty-six cadaver kidney transplants (KTX) were divided into four groups: group 1, day 7 after KTX, stable (n=30); group 2, day 7 after KTX, 8+/-4.5 days before acute rejection (n=12); group 3, first day of acute rejection (n=17); and group 4, day 14 after KTX, stable (n=32). Patients from groups 1 and 4 remained rejection-free for the first 6 months. All rejection episodes were confirmed by core renal biopsy. FNAB samples were cultured according to our published methodology, and culture supernatants were collected at 48 hr and analyzed by ELISA for IL-1beta, sIL-1RII, TNF-alpha, sTNFRI, sTNFRII, and LIF. Serum levels for sIL-1RII, sTNFRI, and sTNFRII were also measured. RESULTS: FNAB cultures from groups 1 and 4 synthesized significantly lower amounts of sTNFRI and sTNFRII than those from either groups 2 or 3. Both sTNFRI and sTNFRII reached high positive and negative predictive values for acute rejection. IL-1beta and sIL-1RII were synthesized by all groups but without differences. No trace of LIF and TNF-alpha was found. sTNFRII was significantly higher in serum from group 3. CONCLUSIONS: Both TNF receptors were positively associated with acute rejection and were good predictors of impending acute rejection. The ratio of sIL-1RII over IL-1 (together with IL-1ra that we previously measured in FNAB cultures) suggests that IL-1 actions may be inhibited with current immunosuppression early after transplantation.

Acute Disease↗

PubMed2001

Hypertension in the elderly.

Both systolic and diastolic blood pressure increase with advanced age and more than 50% of hypertensive patients are aged above 65 years. Age-related vascular and neuro-humoral changes are important factors leading to the development of hypertension in the elderly and the increase in systolic and diastolic blood pressure with age in any individual is a consequence of the relative change in arterial resistance and stiffness. Therefore, hypertension is predominantly or purely systolic in the elderly both in women and men. The risks of hypertensive patients over the age of 65 years are significant and several trials have provided compelling evidence that treatment of hypertension in the elderly is beneficial in terms of reduced morbidity and mortality. Goal blood pressure should be similar in older and younger patients. Lifestyle modifications are of proven benefit and may be the only therapy needed for stage 1 hypertension. The Sixth report of the JNC recommends diuretics, specifically thiazide diuretics as the initial choice for the treatment of elderly patients without any comorbid conditions. Beta-blockers are less effective than thiazides as first line treatment and may only reduce stroke events. Recently, dihydropiridine calcium antagonists have been advocated as first choice agents for the treatment of hypertension in the elderly and are suitable alternatives when diuretics are ineffective, contraindicated or not tolerated. Newer drugs such as AT1 antagonists are also effective in lowering blood pressure in the elderly but large scale data concerning their protective effects are still lacking.

Age Factors↗

PubMed2001

Heart failure, aging, and renal synthesis of dopamine.

The present study evaluates renal dopaminergic activity in 23 patients with heart failure (HF), 10 age-matched controls, and 10 young subjects during normal-salt (NS) intake and after 8 days of low-salt (LS) intake (patients with HF and age-matched controls only). LS intake produced a marked reduction in urine volume in patients with HF but failed to affect urine volume in age-matched controls. Urinary sodium and fractional excretion of sodium were markedly reduced by LS intake in patients with HF and age-matched controls. Daily urinary excretion of L-3,4-dihydroxyphenylalanine (L-dopa) and dopamine was lower in patients with HF than in age-matched controls. LS intake failed to alter L-dopa and dopamine urinary excretion in control subjects. In patients with HF, LS intake produced a significant decrease in urinary L-dopa excretion, but failed to alter the urinary excretion of dopamine. No significant differences were observed in urinary L-dopa, dopamine, and dopamine metabolite levels between aged controls and young healthy subjects. Urinary dopamine-L-dopa ratios in patients with HF on LS intake (24.5 +/- 7.1) were significantly greater than those with NS intake (11.6 +/- 1.3). Urinary dopamine-L-dopa ratios in old control subjects (LS, 9.7 +/- 1.3; NS, 9.3 +/- 1.1) did not differ from those in young healthy subjects (9.2 +/- 0.8). LS intake produced a marked increase in plasma aldosterone levels in both patients with HF (84.6 +/- 14.4 to 148.2 +/- 20.4 pg/mL; P = 0.0008) and controls (102.1 +/- 13.4 to 151.6 +/- 15.7 pg/mL; P < 0.04). Plasma norepinephrine levels were not significantly affected by LS intake in controls (5.1 +/- 1.62 to 6.3 +/- 1.6 pmol/mL; P = 0.22), but were significantly increased in patients with HF (5.8 +/- 0.8 to 7.1 +/- 0.9 pmol/mL; P = 0.04). In conclusion, patients with HF are endowed with an enhanced ability to take up (or decarboxylate) filtered L-dopa, which might counterbalance the reduced renal delivery of L-dopa, contributing to a relative preservation of dopamine synthesis. This may result as a compensatory mechanism, activated by stimuli leading to sodium reabsorption. Age seems to have no influence on renal dopamine production.

3,4-Dihydroxyphenylacetic Acid↗

PubMed2001

Microemulsion cyclosporin formulation, in contrast to the old formulation, widens the T lymphocyte subsets differences between stable and acute rejection of kidney transplants.

BACKGROUND: The new cyclosporin (CsA) formulation, Neoral, has different pharmacokinetics compared with Sandimmune (SIM). Larger area under the curve (AUC) values with equivalent trough blood values are reached when Neoral is administered at equivalent doses to SIM. Previously, we showed a great diagnostic reliability when using cytofluorometric analysis from fine-needle aspiration biopsy (FNAB) samples. We investigated possible changes brought about by Neoral on lymphocyte subsets and the repercussions on the activation score cut-off for acute rejection, defined under SIM treatment. METHODS: Of 63 patients that received SIM, 40 remained rejection-free and 23 suffered one episode of rejection. Of 52 patients that received Neoral, 38 remained rejection-free. Peripheral blood lymphocytes (PBL) and lymphocytes from FNAB taken on days 7 and 14 post-transplantation and on the first day of acute rejection were analysed by flow cytometry. RESULTS: Trough blood CsA levels were not different between SIM and Neoral treatments. Among rejection-free patients, a significant down-regulation of CD3DR and of CD8DR expression on both graft-infiltrating lymphocytes (GIL) and PBL, and significant up-regulation of naïve T cells on GIL were observed with Neoral. These changes were followed by a significant down-regulation of the activation score with Neoral. Conversely, within the acute rejection group, the activation score was significantly higher with Neoral than with SIM. The activation score performed equally well in Neoral transplants compared with what we had reported with SIM. CONCLUSIONS: Our study indicates that Neoral elicits stronger immunosuppressive effects in stable patients, which eventually should translate into better clinical efficiency. However, when acute rejection supervenes, the treatment breakthrough seems stronger with Neoral. Cytofluorometric studies from FNAB samples showed that diagnostic reliability was maintained at a high level under Neoral therapy.

Antigens, CD↗

PubMed2001

Renal dopaminergic mechanisms in renal parenchymal diseases and hypertension.

The present report addresses the status of the renal dopaminergic system activity in patients afflicted with different renal disorders and in the remnant kidney of uninephrectomized (UNX) rats, based on the urinary excretion of L-DOPA, dopamine and amine metabolites. In renal transplant recipients with good recovery of graft function (group 1, n=11), the daily urinary excretion of DOPAC, but not that of HVA, was found to increase progressively throughout the first 12 days post-transplantation from 698+/-57 nmol in the first day to 3498+/-414 nmol on day 9, and then remained constant until day 12. This resulted in a 6-fold increase in the urinary DOPAC/dopamine ratios. In renal transplant recipients with acute tubular necrosis (group 2, n=8), the urinary levels of dopamine, DOPAC and HVA were approximately 30% of those in group 1. In a group of 28 patients with chronic renal parenchymal disorders, the daily urinary excretion of L-DOPA, free dopamine and dopamine metabolites (DOPAC and HVA) correlated positively with the degree of deterioration of renal function (P<0.01). However, the U(Dopamine/(L)-DOPA) and U(DOPAC/Dopamine) ratios in patients with chronic renal insufficiency were found to be similar to those observed in patients with normal renal function. In 14 IgA nephropathy (IgA-N) patients with near normal renal function, the changes in 24 h mean blood pressure when going from 20 to 350 mmol/day sodium intake correlated negatively with the daily urinary excretion of dopamine (r(2)=0.597, P<0.01). The urinary excretion of L-DOPA and dopamine in IgA-N patients with salt-sensitive (SS) blood pressure was lower than in salt-resistant (SR) patients (P<0.05), irrespective of their daily sodium intake. However, the rise in urinary dopamine output during salt loading (from 20 to 350 mmol/day) was greater (P<0.05) in IgA-N SS patients (21.2+/-2.5% increase) than in SR patients (6.3+/-1.4% increase). Fifteen days after the surgery, uninephrectomy (UNX) in the rat was accompanied by an enhanced (P<0.05) urinary excretion of dopamine (36+/-3 vs 26+/-2), DOPAC (124+/-11 vs 69+/-6) and HVA (611+/-42 vs 354+/-7) (nmol/g kidney/kg body weight). This was accompanied by an increase in V(max) values for renal aromatic L-amino acid decarboxylase in the remnant kidney of UNX rats (P<0.05). Sch 23390, a D1 dopamine receptor antagonist, produced a marked reduction in the urinary excretion of sodium in UNX rats, whereas in sham-operated rats the decrease in urinary sodium did not attain a significant difference. It is concluded that the study of the renal dopaminergic system in patients afflicted with renal parenchymal disorders should address parameters other than free urinary dopamine, namely the urinary excretion of L-DOPA and dopamine metabolites (DOPAC and HVA). It is also suggested that in SS hypertension of chronic renal parenchymal diseases, renal dopamine produced in the residual tubular units may be enhanced during a sodium challenge, thus behaving appropriately as a compensatory natriuretic hormone.

3,4-Dihydroxyphenylacetic Acid↗

PubMed2001

Neurohormonal activation, the renal dopaminergic system and sodium handling in patients with severe heart failure under vasodilator therapy.

The benefits of tailoring therapy with vasodilators in patients with severe heart failure are well documented, but this may lead to neurohormonal activation and sodium retention. Renal dopamine has local natriuretic actions and interacts with other hormones involved in renal sodium handling. The aim of the present work was to determine the effects of arterial underfilling induced by vasodilator therapy on renal sodium handling, neurohormonal activation and the activity of the renal dopaminergic system in patients with severe heart failure. For this purpose we monitored haemodynamic parameters, plasma levels of type B natriuretic peptide (BNP), catecholamines, aldosterone, renin activity (PRA), sodium and creatinine, and urinary excretion of sodium, creatinine, L-DOPA, dopamine and its metabolites, before initiation of sodium nitroprusside therapy and every 6 h thereafter (for 42 h), and again after 5 days of angiotensin-converting enzyme (ACE) inhibition, in 10 male patients with severe heart failure. The results of nitroprusside therapy were a marked increase in cardiac index and a substantial decrease in systemic vascular resistance index. Plasma levels of BNP decreased significantly, while PRA, noradrenaline and aldosterone showed marked increases, resulting in a substantial reduction in urinary sodium excretion. Creatinine clearance was not affected. Urinary dopamine and dopamine metabolites increased in response to nitroprusside therapy. After 5 days of ACE inhibition, urinary sodium returned to baseline values, while urinary dopamine was markedly reduced. These results suggest that the renal dopaminergic system is activated in patients with severe heart failure by stimuli leading to sodium renal reabsorption.

Aged↗

PubMed2000

Renal dopaminergic mechanisms in renal parenchymal diseases, hypertension, and heart failure.

The recovery of renal function in renal transplant recipients is accompanied by an enhanced ability to synthesize dopamine (DA), which may contribute to maintain sodium homeostasis. Patients suffering from chronic renal parenchymal disease, a well-recognized form of salt sensitive (SS) hypertension, have a reduced ability to produce DA that correlates well with deterioration of renal function. In patients afflicted with IgA nephropathy, but normal renal function, urinary excretion of DA correlated positively with BP responses to changes from 200 to 20 mmol/day salt intake. In black salt resistant (SR) normotensives (NT) and SR hypertensives, under low salt intake (40 mmol/day), but not SS-NT and SS-HT, the saline infusion induced increments of DA and DOPAC urinary excretion correlated significantly with increments of sodium urinary excretion and sodium fractional excretion. Patients afflicted with heart failure (HF) have a reduced delivery of L-DOPA to the kidney, accompanied by an increase in DA/L-DOPA urinary ratios. This suggests that HF patients have an increased ability to take up or decarboxylate L-DOPA. Sodium restriction resulted in a significant decrease in urinary L-DOPA, DA and DOPAC in HF patients, suggesting that the system responds to sodium. It is concluded that activity of renal dopaminergic system may be altered in SS subjects, despite the level of their BP, and an enhanced delivery of L-DOPA to the kidney may be beneficial in edema formation states.

3,4-Dihydroxyphenylacetic Acid↗

PubMed2000

Salt intake and sensitivity of intestinal and renal Na+-K+ atpase to inhibition by dopamine in spontaneous hypertensive and Wistar-Kyoto rats.

The present study evaluated the activity of jejunal Na+-K+-ATPase and its sensitivity to inhibition by dopamine in spontaneous hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats during low (LS), normal (NS) and high (HS) salt intake. Basal jejunal Na+-K+-ATPase activity in SHR on LS intake was higher than in WKY rats. Jejunal Na+-K+-ATPase activity in WKY rats, but not in SHR, on LS intake was significantly reduced (20% decrease) by dopamine (1 microM) and SKF 38393 (10 nM), but not quinerolane (10 nM), this being antagonized the D1 receptor antagonist (SKF 83566). Changing from LS to NS or HS intake in WKY rats increased basal jejunal Na+-K+-ATPase activity and attenuated the inhibitory effect of dopamine. In SHR, changing from LS to NS or HS intake increased basal jejunal Na+-K+-ATPase activity. Basal renal Na+-K+-ATPase activity in SHR on LS intake was similar to that in WKY rats and was insensitive to inhibition by dopamine. Changing from LS to NS or HS intake in WKY rats increased basal renal Na+-K+-ATPase activity without affecting the inhibitory effect of dopamine. In SHR, changing from LS to NS or HS intake failed to alter basal renal Na+-K+-ATPase activity. It is concluded that inhibition of jejunal Na+-K+ ATPase activity by D1 dopamine receptor activation is dependent on salt intake in WKY rats, and SHR animals fail to respond to dopamine, irrespective of their salt intake.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗

PubMed2000

Concerted action of dopamine on renal and intestinal Na(+)-K(+)-ATPase in the rat remnant kidney.

The present study evaluated renal and intestinal adaptations in sodium handling in uninephrectomized (Unx) rats and the role of dopamine. Two weeks after uninephrectomy, the remnant kidney in Unx rats weighed 33 +/- 2% more than the corresponding kidney in sham-operated (Sham) animals. This was accompanied by increases in urinary levels of dopamine and major metabolites [3, 4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid] and increases in maximal velocity values (169 vs. 115 nmol. mg protein(-1). 15 min(-1)) for renal aromatic L-amino acid decarboxylase, the enzyme responsible for the synthesis of renal dopamine. High salt (HS) intake increased (P < 0.05) the urinary excretion of dopamine and DOPAC in Unx and Sham rats. However, the urinary levels of L-3,4-dihydroxyphenylalanine, dopamine, and DOPAC in Sham rats during HS intake were lower than in Unx rats. Blockade of dopamine D(1) receptors (Sch-23390, 2 x 30 microg/kg) reduced the urinary excretion of sodium in Unx (31% decrease) more pronouncedly than in Sham (19% decrease) rats. However, inhibition of renal Na(+)-K(+)-ATPase activity by dopamine was of similar magnitude in Unx and Sham rats. In parallel, it was observed that uninephrectomy resulted in a significant reduction in jejunal sodium absorption and Na(+)-K(+)-ATPase activity in jejunal epithelial cells. In jejunal epithelial cells from Sham rats, dopamine (1 microM) failed to inhibit Na(+)-K(+)-ATPase activity, whereas in Unx rats it produced a significant reduction. It is concluded that uninephrectomy results in increased renal dopaminergic activity and dopamine-sensitive enhanced natriuresis. Furthermore, it is suggested that decreased jejunal absorption of sodium may take place in response to partial renal ablation, as an example of renal-intestinal cross talk.

3,4-Dihydroxyphenylacetic Acid↗

PubMed2000

Renal synthesis of dopamine in asymptomatic post-infarction left ventricular systolic dysfunction.

Left ventricular systolic dysfunction (LVSD) following acute myocardial infarction (AMI), by decreasing renal blood flow, may interfere with renal L-DOPA availability and, consequently, dopamine synthesis. Dopamine of renal origin exerts local natriuretic effects. We studied 17 post-AMI patients with asymptomatic LVSD (ejection fraction < 40%) and 14 without (ejection fraction > or = 40%), measuring 24-h urinary excretions of L-DOPA, dopamine and its metabolites, and plasma levels of the amines, amine derivatives and type-B natriuretic peptide (BNP). Baseline characteristics were well balanced between the two groups. No differences were observed in urinary volume and sodium and creatinine excretions. The group with asymptomatic LVSD presented lower urinary excretion of L-DOPA (66.8 +/- 10.1 versus 115.3 +/- 21.9 nmol x day(-1), P = 0.04), whereas plasma levels of L-DOPA were identical in both groups. Urinary dopamine was similar in the two groups (1124.2 +/- 172.4 versus 1049.0 +/- 146.4 nmol x day(-1), P = 0.86), resulting in higher urinary dopamine/L-DOPA ratios in patients with asymptomatic LVSD (20.4 +/- 3.0 versus 9.9 +/- 0.8, P < 0.001). Plasma levels of BNP were higher in the asymptomatic LVSD group (348.5 +/- 47.3 versus 146.8 +/- 21.9 microg x ml(-1), P = 0.003). Ejection fraction was negatively correlated with both plasma levels of BNP and urinary dopamine/L-DOPA ratios. Renal dopamine production is well preserved in patients with asymptomatic LVSD and increased neurohumoral activation, despite reduced urinary excretion of its precursor. This suggests that renal uptake and/or decarboxylation of L-DOPA is enhanced in this condition, as a compensatory mechanism, contributing to preservation of urinary sodium excretion.

Dopamine↗

PubMed1999

Acute hypotensive, natriuretic, and hormonal effects of nifedipine in salt-sensitive and salt-resistant black normotensive and hypertensive subjects.

In a randomized double-blind study, we compared the short-term effects of nifedipine (10 mg 3x daily for 1 day) versus placebo on 24-h blood pressure, diuresis, natriuresis, urinary excretion of dopamine and metabolites, and on plasma renin activity (PRA) and plasma aldosterone levels in 18 black hypertensive (HT) patients [eight salt-resistant (HT-SR) and 10 salt-sensitive (HT-SS)], and in 20 black normotensive (NT) subjects (12 NT-SR and eight NT-SS) who were studied randomly with both a high- (HS) and a low-salt (LS) diet. In comparison to placebo, nifedipine significantly decreased 24-h mean BP in all groups either with HS or LS diets (all p<0.05). With HS, greater hypotensive effects were achieved in NT-SS (-10+/-2 mm Hg) versus NT-SR (-3+/-1 mm Hg; p<0.05) and in HT-SS (-18+/-2 mm Hg) versus HT-SR (-12+/-2 mm Hg; p<0.05). In NT-SS and HT-SS, nifedipine induced greater (p<0.05) BP decrease with HS (-10+/-2 and -18+/-2 mm Hg) than with LS (-4+/-1 and -9+/-1 mm Hg, respectively), whereas in NT-SR and HT-SR, the hypotensive effect did not differ between HS and LS. Nifedipine versus placebo significantly increased natriuresis and fractional excretion of sodium in all groups only with HS (p<0.05) but not with LS diets. Only in HT-SS were the hypotensive and natriuretic effects of nifedipine significantly correlated (r = -0.77; p<0.01). Nifedipine produced a similar increase of the urinary excretion of dopamine, L-DOPA, and of DOPAC in all subjects, which did not correlate with hypotensive and natriuretic effects. Nifedipine did not modify plasma levels of renin and of aldosterone except in NT-SS with HS, in whom nifedipine increased PRA levels (p <0.05). We conclude that although nifedipine reduces BP in all groups of NT and HT with LS and HS diets, the effect is greater in salt-sensitive subjects with HS. Although in HT-SS with HS, the short-term natriuretic response to nifedipine may contribute to its hypotensive effects, the diuretic-natriuretic effect of nifedipine is not necessary for the expression of its hypotensive effect. Moreover, it is unlikely that any short-term effects of nifedipine either on the renal dopaminergic system or on the secretion of aldosterone explain nifedipine short-term hypotensive and diuretic-natriuretic effects.

Adult↗

PubMed1999

Aging, high salt intake, and renal dopaminergic activity in Fischer 344 rats.

The present study examined renal dopaminergic activity and its response to high salt (HS) intake in adult (6-month-old) and old (24-month-old) Fischer 344 rats. Daily urinary excretion of L-3, 4-dihydroxyphenylalanine (L-DOPA), dopamine, and its metabolites 3, 4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid was similar in adult and old rats; by contrast, daily urinary excretion of norepinephrine in old rats was almost twice that in adult animals. HS intake (1% NaCl) over a period of 24 hours resulted in a 2-fold increase in the urinary excretion of dopamine, DOPAC, and norepinephrine in adult animals but not in old animals. Norepinephrine and L-DOPA plasma levels did not change during HS intake and were similar in both groups of rats. The natriuretic response to an HS intake in old rats (from 4.7+/-0.4 to 10.7+/-2.0 nmol. kg(-1). d(-1); Delta=6.0+/-0.9 nmol. kg(-1). d(-1)) was less than in adult rats (from 5.2+/-0.4 to 13.5+/-2.5 nmol. kg(-1). d(-1); Delta=8.3+/-0.8 nmol. kg(-1). d(-1)). A diuretic response to HS intake was observed in adult rats (from 20.9+/-2.3 to 37.6+/-2.8 mL. kg(-1). d(-1)) but not in old rats (from 37.7+/-5.7 to 42.3+/-6. 0 mL. kg(-1). d(-1)). Dopamine levels and dopamine/L-DOPA ratios in the renal cortex of old rats were greater than in adult rats. HS intake increased both dopamine levels and dopamine/L-DOPA ratios in the renal cortex of adult rats but not in old rats. Aromatic L-amino acid decarboxylase activity was higher in old rats than in adult rats; HS intake increased L-amino acid decarboxylase activity (nmol. mg protein(-1). l5 min(-1)) in adult rats (from 67+/-1 to 93+/-1) but not in old rats (from 86+/-2 to 87+/-2). Dopamine inhibited Na(+),K(+)-ATPase activity in proximal tubules obtained from adult rats, but it failed to exert such an inhibitory effect in old rats. It is concluded that renal dopaminergic tonus in old rats is higher than in adult rats but fails to respond to HS intake as observed in adult rats. This may be due in part to the inability of dopamine to inhibit Na(+),K(+)-ATPase activity in old rats.

3,4-Dihydroxyphenylacetic Acid↗