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Biomedical subjects

M Martínez-Maldonado

Publications and source records attributed to M Martínez-Maldonado.

At least 19 recordsLinked to original sources
PubMed2001

Role of hypertension in the progression of chronic renal disease.

Hypertension leads to renal disease through a series of mechanisms that seem to be exaggerated in African-Americans, who have a higher prevalence of both hypertension and end-stage renal disease than whites. Renal disease itself leads to hypertension, which in turn can contribute to progression of renal disease. Although there are numerous mechanisms involved in the process of renal disease progression, the renin-angiotensin system plays a major role as determined by the beneficial response to angiotensin I-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (AT II blockers) of reduced rate of progression in a variety of clinical and experimental renal diseases. Macromolecular trafficking across the glomerulus leading to proteinuria plays a significant role in progression of chronic renal disease. Reversal of this abnormality and reduced stress on capillary walls may be the major mechanisms of beneficial action of ACEIs and AT II blockers in halting renal disease progression.

Black or African American↗
PubMed1998

Hypertension in end-stage renal disease.

Patients with moderate to severe renal disease have a very high incidence of hypertension. In end-stage renal disease (ESRD) this is true regardless of the nature of the underlying renal disease. Nevertheless, patients with glomerular diseases and autosomal dominant polycystic kidney disease are particularly vulnerable. Evidence is presented that ESRD hypertension is the result of extracellular volume expansion, increased or inappropriate response of the renin-angiotensin system and overactivity of the sympathetic system. In addition, the role of endothelin-1, nitric oxide and other vasodilators, and abnormal ion channels in generating high blood pressure, is considered.

Humans↗
PubMed1996

Atheroembolic renal disease.

Atheroembolic renal disease is an important and often underdiagnosed cause of renal insufficiency in the elderly. Renal damage results from embolization of cholesterol crystals from atherosclerotic plaques in large vessels such as the abdominal aorta to small arteries of the kidney. The typical patient is a white man older than 60 years who has an insidious increase in serum creatinine levels after an arteriographic procedure or vascular surgery. Renal outcome ranges from partial recovery of kidney function to end stage renal disease requiring replacement therapy. Tissue injury from cholesterol crystal embolization is not restricted to the kidneys but also involves the skin, muscles, abdominal organs, and central nervous system resulting in significant morbidity and mortality. Accurate diagnosis is often made by performing a skin, muscle, or renal biopsy. Although effective therapy is lacking, heightened awareness of atheroembolic renal disease is necessary for prompt diagnosis and institution of supportive care.

Embolism, Cholesterol↗
PubMed1996

Acute renal failure in the aged.

Acute renal failure (ARF) is frequent in aged individuals. In this article, we review the literature and relate our own experience in this field. It is concluded that there are no technical reasons to deny treatment for ARF using any of the available techniques based on age. Attempts to prevent the onset of ARF are important. Prophylaxis may be focused on diligent and adequate diagnosis and treatment of reversible renal hypoperfusion, by far the most common cause of pre-renal ARF in the elderly. Administration of potentially nephrotoxic drugs should be avoided, but when necessary creatinine clearance (as the marker of glomerular filtration) rather than blood creatinine levels should be used to establish the appropriate dose. In the elderly, azotemia or other consequences of ARF may induce acute behavioral changes that are almost always reversible; treatment should not be stopped on the false assumption that the patient's mental status is irreversible.

Acute Kidney Injury↗
PubMed1995

Role of angiotensin II in the expression and regulation of transforming growth factor-beta in obstructive nephropathy.

Unilateral ureteral obstruction (UUO) leads to fibrosis of the obstructed kidney. We tested the hypothesis that interstitial fibrosis in UUO results, at least in part, from enhanced expression of transforming growth factor-beta (TGF-beta) which in turn is regulated by local angiotensin II (Ang II) generation. (The generic name TGF-beta is used to discuss properties shared by all isoforms, but special reference to other isoforms is made when specifically needed.) Using Northern blot and immunohistochemical analysis, we examined the expression of TGF-beta in rat kidneys after 24 hours (aUUO) and one week (cUUO) of obstruction. Obstructed kidneys from both periods had increased interstitial and perivascular TGF-beta immunoreactivity compared to contralateral and sham kidneys, in which immunostaining was confined to the inner medulla. Relative abundance of all TGF-beta mRNA isoforms were higher in the obstructed than in contralateral and sham kidneys in both aUUO and cUUO. Expression of TGF-beta isoforms varied according to site (cortex vs. medulla), segment of the nephron, type of cells and duration of the obstruction. The increase in TGF-beta immunoreactivity and mRNA levels in aUUO and cUUO was almost totally abolished by pretreatment with losartan. We conclude that in UUO: (a) TGF-beta gene expression is increased and differentially regulated; (b) Ang II, at least partially, mediates the overexpression of TGF-beta gene; and (c) Ang II may play a central role in fibrogenesis in this and other models of tubulointerstitial disease.

Angiotensin II↗
PubMed1995

Sequential changes in renal expression of renin-angiotensin system genes in acute unilateral ureteral obstruction.

Unilateral ureteral obstruction (UUO) alters the expression of genes encoding for the renin-angiotensin system (RAS). We tested the hypothesis that changes in RAS genes expression occur soon after obstruction. Indeed, measurements during the first 24 hours of UUO showed up-regulation of renin mRNA in the obstructed kidney at 1 hour. UUO also led to increases in PRA and renal renin content, ACE activity and Ang II concentration in the experimental kidney. The obstructed kidney relative abundance of renin mRNA was increased compared to basal at 1, 2, 6, and 24 hours; the contralateral kidney renin mRNA expression was reduced. AT1-R mRNA expression was diminished at 6 and 24 hours in the obstructed kidney compared to contralateral and sham kidneys. ACE activity was up-regulated in the obstructed kidney and transiently down-regulated in the contralateral kidney. These findings show for the first time that activation of the RAS results from as little as 1 hour of UUO and that up-regulation of renin mRNA and ACE activity lead to increase Ang II production which down-regulates AT1-R mRNA as early as 6 hours post-UUO. These studies establish a pattern of sequential, differential regulation of the RAS genes in acute UUO that provide an explanation for the hemodynamic changes in this condition.

Acetylcholinesterase↗
PubMed1993

Mechanisms of ozolinone-induced renin release and diuresis.

Dextrorotatory (+) and levorotatory (-) ozolinone (ozo) were injected directly into the left renal artery of volume-expanded anesthetized dogs. (+)Ozo (40 micrograms/kg/min) had no effect on urine flow and fractional excretion of Na+, Cl-, or K+ when compared with the basal period. Comparison of (-)ozo to (+)ozo revealed the following: urine flow 4.0 +/- 0.3 v 0.9 +/- 0.1 mL/min (P < .001); FENa+ 29.8 +/- 3.0 v 5.6 +/- 0.3% (P < .001); FECl- 35.7 +/- 4.1 v 5.8 +/- 0.4% (P < .001); FEK+ 87 +/- 4 v 49 +/- 5% (P < .001). Glomerular filtration rate (GFR) and renal plasma flow (RPF) did not change. The renin secretory rate (RSR) was significantly higher with (-)ozo than with (+)ozo (498 +/- 113 v 210 +/- 53 ng A I/mL/hr.mL/min). Moreover, (-)ozo significantly increased urine PG excretion compared to basal values: 466 +/- 63 v 263 +/- 30 pg/min (P < .05). Indomethacin (2 mg/kg) markedly blunted the effects of (-)ozo on PG and RSR, and completely abolished the rise in PRA. (+)Ozo had no significant effect on urine PG excretion. Neither (-)ozo nor (+)ozo had an effect on renin production in isolated glomeruli. By contrast, (-)ozo but not (+)ozo increased PGE2 synthesis in papillary and medullary slices. The data are consistent with the proposal that the effect of (-)ozo on renin secretion and PRA is through a PG-dependent mechanism, and that it requires an intact macula densa mechanism.

Animals↗
PubMed1993

Internal cRNA standards for quantitative northern analysis.

We report a simple method using copy RNA (cRNA) internal standards for quantitative Northern hybridization. This was accomplished by synthesis of a full-length or "half"-length cRNA and mixing these RNA internal standards with samples to be tested for the abundance of a given mRNA. Both full-length and truncated cRNAs are detected in Northern analysis by the nucleic acid detection probe (which can be labeled with 32P or biotin), and the known amount of the truncated cRNA is compared to the homologous mRNA present in the specimen being examined. We demonstrate the usefulness of this method by measuring the expression of renin in rat kidney with ureteral obstruction and angiotensin II receptor (AT1-R) mRNA in kidneys from spontaneously hypertensive rats. It was found that this method of preparing cRNA internal standards successfully controlled for variables (such as differences in loading, transfer and hybridization efficiency) that often frustrate efforts to use Northern analysis as a quantitative tool and enabled direct estimation of absolute mRNA amount present in samples. This technique may have wide applicability and permit a more quantitative use of Northern analysis.

Animals↗
PubMed1992

Renal hemodynamics and urinary concentrating capacity in protein deprivation: role of antidiuretic hormone.

The role of antidiuretic hormone (ADH) in the renal concentration defect and hemodynamic changes in protein malnutrition was evaluated in rats with diabetes insipidus (DI) after 2 weeks of low protein feeding. Free water reabsorptive capacity (TcH2O), glomerular filtration rate (GFR), and renal plasma flow (RPF) were measured in the protein deprived rats and in DI rats fed a normal protein diet. The effect of urea supplementation of the low protein diet on renal concentrating capacity was also evaluated. In addition, the renal hemodynamic response to acute administration of ADH was measured and correlated with changes in plasma renin concentration and renal renin content (RRC). Protein deprivation in DI rats resulted in reduced urine osmolality and urea excretion, differences which were reversed by urea supplementation. Protein deprivation did not affect free water reabsorptive capacity but did reduce GFR and RPF. Acute ADH administration significantly increased GFR and RPF in protein-deprived rats; these changes were associated with a reduction in RRC and release. These results suggest that dietary protein restriction does not directly affect the tubular capacity to generate and reabsorb free water. The hemodynamic changes seen in protein deprivation are not mediated by ADH and may be secondary to increased intrarenal angiotensin II.

Animals↗
PubMed1991

Effects of dopamine-receptor antagonists and renal denervation on amino acid-induced hyperfiltration.

The mechanism whereby an infusion of amino acids (AA) leads to increments in glomerular filtration rate (GFR) and renal plasma flow (RPF) is incompletely understood. Dopamine (DA) is a catecholamine in which known actions at low doses include the ability to increase both GFR and RPF. Furthermore, urinary DA excretion has been shown to be augmented after an oral protein load. We therefore studied the renal hemodynamic response to intravenous infusion of a 10% mixed AA solution in anesthetized euvolemic Wistar-Furth rats in the presence or absence of specific DA1 [Sch 23390 (SCH)] and DA2 [S-sulpiride (S-SP)] receptor antagonists. Infusion of AA in vehicle-pretreated rats resulted in a 28 +/- 8% increase in GFR and a 29 +/- 6% increase in effective ERPF over baseline values. Administration of AA in the presence of SCH also resulted in elevations in both GFR and ERPF by 23 +/- 3% and 26 +/- 6%, respectively. In contrast, when AA were given in the presence of S-SP, the rise in both GFR and ERPF was completely prevented. To examine whether the AA-induced hyperfiltration was due to DA release from renal nerves or enhanced renal tubule DA synthesis, we administered AA to rats in which the left kidney had been chronically denervated while the right kidney remained intact. Infusion of AA led to significant increments in GFR (33 +/- 4%) and ERPF (34 +/- 7%) only in the intact control kidney, whereas GFR and ERPF remained unaltered in the denervated kidney.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acids↗
PubMed1990

Lenticular rubidium uptake and plasma renin activity in weanling cataract-prone salt-sensitive rats.

Our earlier studies of cataracts in Dahl salt-sensitive (DS) rats suggested the possibility of altered lens ion transport as a contributing factor in cataractogenesis in this genetic model. We also observed that those weanling DS rats with the greatest pressor response to a high salt diet eventually developed cataracts, and that changes in salt intake modified cataract formation. In the present studies, we measured lens 86Rb uptake as an index of sodium-potassium adenosine triphosphatase [(Na+,K+)-ATPase] activity in weanling DS rats before the development of cataracts or sustained hypertension. Additionally, plasma renin activity was measured to indirectly assess our hypothesis that the difference between cataract-prone DS rats and DS rats unlikely to develop cataracts might be a difference in degree of salt sensitivity. At the age of 4 weeks, 50 DS and 25 salt-resistant (DR) rats were given a high sodium diet for 2 weeks, at which time the rats were divided into three groups based on the systolic blood pressure response, that is, cataract-prone DS rats with systolic blood pressure equal to or greater than 155 mm Hg, DS rats unlikely to develop cataracts with systolic blood pressure less than or equal to 125 mm Hg, and DR rats. Lens and aqueous humor Na+ and K+, lens dry weight, and water content were not significantly different among the three groups of weanling rats. Plasma renin activity was lowest in cataract-prone DS rats and low in DS rats unlikely to develop cataracts when compared with values in DR rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Role of macula densa in diuretics-induced renin release.

Diuretic therapy may enhance renin release by various mechanisms, principally contraction of extracellular fluid volume and its effects, including a fall in arterial pressure. Awake hydropenic or volume-expanded rats received diuretics (amiloride and hydrochlorothiazide) that are known inhibitors of NaCl transport beyond the macula densa; also the well-known Na(+)-K(+)-2 Cl- transport system inhibitor furosemide was administered. We also evaluated the effect of a dose of ethacrynic acid (a drug that shares the same mechanism of action as furosemide but is not diuretic in the rat). The direct action of the diuretics on renin-producing cells was examined in isolated glomeruli; a rise in renin release was observed with the calmodulin inhibitor trifluoperazine (10(-5) M). Renin release in intact hydropenic rats was not altered by diuretic therapy, but furosemide increased plasma renin activity in hydropenic as well as in volume-expanded rats. This demonstrates the importance of furosemide inhibition of transport in the macula densa for its renin secretory action. None of the diuretics (amiloride, hydrochlorothiazide, ethacrynic acid, or furosemide) elicited changes in renin release from glomeruli (10(-6) to 10(-3) M); amiloride and hydrochlorothiazide (10(-4) to 10(-3) M) did not change renin release from slices, but 10(-3) M ethacrynic acid and furosemide increased renin secretion in this preparation. This suggests that an effect on the macula densa is essential in loop diuretic-mediated renin release.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Hyperuricemia, gout, and autosomal dominant polycystic kidney disease.

The relationship between hyperuricemia, gout, and autosomal dominant polycystic kidney disease (ADPKD) is not widely recognized. In an attempt to further clarify this relationship, the authors have studied 17 patients with ADPKD, 9 controls, 9 patients with proven gout and chronic renal failure, 11 patients with gout and normal renal function, and 11 patients with chronic renal failure. The mean serum uric acid concentration was higher in patients with ADPKD as a group than in controls (8.0 +/- 1.7 mg/dl vs. 6.4 +/- 1.6 mg/dl, p less than .02). Clinical gout was identified in 24% of patients with ADPKD; none of the patients with chronic renal failure of other etiologies had gout. Fractional excretion of uric acid and the activity of the enzyme hypoxanthine guanine phosphoribosyl transferase (HGPRT) were not different among the groups studied. From this study the authors conclude that ADPKD should be included among those diseases associated with hyperuricemia and gout. A partial deficiency in HGPRT or abnormal renal handling of uric acid do not appear to be responsible for the increased incidence of gout in patients with ADPKD.

Aged↗
PubMed1989

Renal and systemic effects of short-term high protein feeding in normal rats.

Various studies have shown that a high protein (HP) diet, compared to a low protein (LP) diet, leads to hypercalciuria and alterations in renal and systemic hemodynamics. The authors compared the effects of HP diet to those of normal protein diet (NP) to determine the possible mechanisms by which changes in systemic hemodynamics and hypercalciuria occurred. The studies were conducted in awake rats; the effects of dietary sodium content on the changes induced by HP also were evaluated. The relationship of prostaglandins (PG), renin (PRA), and aldosterone (PA) to changes in blood pressure (BP) was assessed. Two weeks after HP and normal sodium feeding (40%), glomerular filtration rate (GFR) and urine flow (V) were not different from the same values in a group on an NP diet (23%). When HP was fed with low sodium, there was a rise in V as a consequence of greater fluid intake. Although plasma calcium remained constant, the hypercalciuria correlated with high protein and sodium content. Alterations in 1,25(OH)2 vitamin D3 or PTH (cyclic AMP excretion) function did not explain the hypercalciuria induced by HP. This suggests that HP leads to inhibition of tubular calcium reabsorption by mechanism(s) yet to be elucidated. Although HP did not alter GFR, it led to an increase in BP, a fall in renal vascular resistance, and an increase in RPF, regardless of sodium intake. PRA and urine PGE2 excretion were significantly higher in the rats on HP diet, whereas PA remained unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Functional studies in experimental renal cortical necrosis in the rat.

Necrosis of the outer two-thirds of the cortex (CN) was induced with boiling water in the left kidney of rats. Two days afterward, morphological damage was shown to be limited to the superficial cortex; deep nephron population was well-preserved. Glucose reabsorption under basal and glucose loading conditions, and extraction of p-aminohippurate, used as indices of proximal tubule integrity, were normal in control and experimental kidneys 48 h after cortical necrosis. Basal fractional water and electrolyte excretion did not differ between control and experimental kidneys. Calculated mean single-nephron glomerular filtration rate (GFR) and plasma flow for superficial (SupGFR and SupNPF) and juxtamedullary nephrons (JMGFR and JMPF) were similar to those obtained by micropuncture and Hanssen's technique for SupGFR, and for JMGFR by Hanssen's. Volume expansion led to a 27% increase in calculated SupGFR, but no change in JMGFR. The JMPF increased by 81%, whereas SupNPF increased by only 23%, suggesting that, in this model, GFR of deep nephrons may be independent of plasma flow. The results indicate that deep nephrons retain their functional integrity 48 h after cortical necrosis. After volume expansion fractional excretion of sodium was greater, and fractional water reabsorption less, in CN than in control kidneys. Thus handling of sodium and water by superficial and deep nephrons under basal conditions was similar, but reabsorptive capacity for deep nephrons of CN was lower during volume expansion. The present studies suggest that deep nephrons can maintain relatively normal function in cortical necrosis.

Animals↗
PubMed1989

Prevention and reversal of cataracts in genetically hypertensive rats through sodium restriction.

We previously described the Dahl salt-sensitive rat as a potential model of cataractogenesis in which cataract formation is associated with hypertension. Cataractous lesions were characterized by a marked lenticular and aqueous humor electrolyte imbalance. In the present study the effects of chronic dietary sodium restriction on cataract formation were evaluated in salt-sensitive rats to determine whether or not modification of the hypertensive process might reduce the incidence of cataracts in this genetic model. In addition, the possibility that early cataractous lesions in adult hypertensive salt-sensitive rats might be reversed by acute sodium restriction was evaluated. Chronic dietary sodium restriction modified the development of hypertension and prevented cataract formation in salt-sensitive rats. Furthermore, acute dietary sodium restriction (1 week) completely and consistently reversed early cataractous lesions (pinpoint opacities) in adult hypertensive salt-sensitive rats. Both the prevention and reversal of cataracts were associated with normalization of the lenticular and aqueous humor parameters measured. These data suggest that cataractogenesis is not the consequence of sustained arterial hypertension, but rather that initiation of both hypertension and cataract formation in this genetic model may be the result of extracellular fluid volume state.

Aging↗