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Biomedical subjects

L A Sechi

Publications and source records attributed to L A Sechi.

At least 91 records · Page 5Linked to original sources
PubMed1996

Phosphodiesterase inhibitors correct resistance to natriuretic peptides in rats with Heymann Nephritis.

Experimental nephrotic syndrome is characterized by abnormal sodium metabolism, reflected in a blunted natriuretic response both to volume expansion and to infused atrial natriuretic peptide (ANP). The studies presented here examined the relationships among plasma ANP concentration and urinary sodium (VNaV) and cyclic GMP excretion (UcGMPV) in vivo, and the responsiveness of isolated glomeruil and inner medullary collecting duct (IMCD) cells to ANP and urodilatin (renal natriuretic peptide; RNP) in vitro in rats with Heymann nephritis, an immunologically mediated model of nephrotic syndrome. Nine to 14 days after Ip injection of anti-Fx1A antiserum, rats were proteinuric and had a blunted natriuretic response to intravenous infusion of isotonic saline (2% body weight, given over 5 min). Thirty min after the onset of the infusion, plasma ANP concentration was increased to the same extent in both normal and nephritic rats, compared with their respective hydropenic controls. Despite this increase, UcGMPV was significantly less in nephritic rats after the saline infusion. Accumulation of cGMP by isolated glomeruil and IMCD cells from nephritic rats after incubation with ANP and RNP was also significantly reduced, compared with normal rats. This difference was not related to differences in either density or affinity of renal ANP receptors, but was abolished when accumulation of cGMP was measured in the presence of 10(-3) M isobutylmethylxanthine or Zaprinast, two different inhibitors of cyclic nucleotide phosphodiesterases (PDE). Infusion of Zaprinast into one renal artery in nephritic rats normalized both the natriuretic response to volume expansion and the increase in UcGMPV from the infused, but not the contralateral, kidney. Furthermore, cGMP-PDE activity was increased in IMCD cell homogenates from nephritic compared with normal rats (388 +/- 32 versus 198 +/- 93 pmol/min per mg protein, P < 0.03). These results indicate that blunted volume expansion natriuresis accompanied by cellular resistance to ANP in vitro occurs in an immunologic model of renal injury. The resistance is not related to an alteration in ANP release or binding to its renal receptors, but is suppressed by PDE inhibitors and is associated with increased renal cGMP. PDE activity, thus suggesting that enhanced cGMP-PDE activity may account for resistance to the natriuretic actions of ANP observed in vivo. This defect may represent the intrinsic sodium transport abnormality linked to sodium retention in nephrotic syndrome.

1-Methyl-3-isobutylxanthine↗
PubMed1996

Molecular mechanisms of insulin resistance in arterial hypertension.

The associations between insulin resistance, hyperinsulinaemia, and hypertension are well recognized. Hyperinsulinaemia induces hypertension through increased renal tubular reabsorption of sodium and water, increased sympathetic nervous system activity, proliferation of vascular smooth muscle cells, and alterations of transmembrane cation transport. At physiological concentrations, insulin decreases urinary sodium excretion, an action mediated by binding to specific high-affinity receptors. Insulin resistance is present also in strains of rats with genetic hypertension (spontaneously hypertensive and Dahl salt-sensitive rats) that can be utilized as models to study the molecular mechanisms of this abnormality. In normal rats, the number and mRNA levels of insulin receptors in the kidney are inversely related with dietary sodium content, suggesting the existence of a feedback mechanism that limits insulin-induced sodium retention when extracellular fluid volume is expanded. We have investigated the relationships between dietary sodium intake and renal insulin receptors in spontaneously hypertensive rats and have found that in this strain the feedback mechanism is abolished. In addition, spontaneously hypertensive rats have decreased expression of the insulin receptor gene in the liver and decreased receptor autophosphorylation and phosphorylation of an endogenous substrate (IRS-1) in liver and muscle. These observations provide a potential explanation for the decreased sensitivity to insulin present in spontaneously hypertensive rats. In these rats, the loss of the capability to down-regulate insulin receptor in the kidney when extracellular fluid volume is expanded can lead to further sodium retention and might play a role in the development and maintenance of hypertension.

Animals↗
PubMed1995

Abnormalities of autonomic nervous system in hyperadrenergic orthostatic hypotension: description of a case.

Hyperadrenergic orthostatic hypotension was diagnosed in a 27-year-old man because of recurrent episodes of hypotension associated with high plasma noradrenaline levels. In this patient, laboratory tests were performed to evaluate autonomic nervous system function. Decreased response to Valsalva maneuver and carotid sinus massage indicated decreased baroreflex and vagal responsiveness, respectively. Cardiovascular response to the handgrip was reduced in comparison to controls. Passive leg raise showed normal reduction of plasma norepinephrine, indicating normal responsiveness of cardiopulmonary receptors. 'Non-dipper' profile in the ambulatory blood pressure monitoring provided further evidence for an impaired autonomic control of cardiovascular function in this patient. This report suggests the presence of autonomic dysfunction in hyperadrenergic orthostatic hypotension.

Adult↗
PubMed1995

Receptors for atrial natriuretic peptide are decreased in the kidney of rats with streptozotocin-induced diabetes mellitus.

To determine whether decreased renal responsiveness to atrial natriuretic peptide (ANP) in diabetes is mediated by alterations in the renal ANP receptor, ANP receptor density and affinity were measured 17-20 d after streptozotocin injection and compared with values in vehicle-treated controls and streptozotocin-treated rats made euglycemic with insulin. Plasma ANP concentration was significantly greater in hyperglycemic diabetic rats than in control or euglycemic diabetic rats. Both in glomeruli and inner medulla, ANP receptor dissociation constant did not differ among the three study groups, whereas the maximum binding capacity was decreased significantly in hyperglycemic diabetics in comparison with controls and euglycemic diabetics. Glomerular clearance receptors were also decreased significantly in hyperglycemic diabetic rats in comparison with control and euglycemic diabetic rats. To determine whether the decreased number of renal ANP receptors in diabetic rats was associated with a decreased biological response, we measured ANP-dependent cyclic GMP (cGMP) accumulation by isolated glomeruli and inner medullary collecting duct cells in vitro. cGMP accumulation was significantly less in hyperglycemic diabetic rats than in controls or euglycemic diabetic rats both in the presence or absence of the phosphodiesterase inhibitor zaprinast. cGMP phosphodiesterase activity in inner medullary collecting duct cells obtained from control and hyperglycemic diabetic rats did not differ. Thus, the decreased number of biologically active ANP receptors in the kidneys of diabetic rats is accompanied by decreased biological responsiveness in vitro and provides a potential explanation for the reduction in renal sensitivity to ANP in this condition.

Animals↗
PubMed1994

Ribosomal RNA gene (rrn) organization in enterococci.

A cloned 1.8-kb probe containing the 3' end of 16S ribosomal RNA and the 5' end of 23S ribosomal RNA from Enterococcus hirae was used to analyze various endonuclease digests of enterococci. In the ATCC strains tested we observed a remarkable conservation of the ApaI sites in the rrn operons, and a partial conservation of EcoRI sites. Using a number of other endonuclease digestions with the ApaI rrn probe, we estimate the number of rrn operons in enterococci to be between five and six.

DNA, Bacterial↗
PubMed1994

Dose-dependence and reversibility of the hemoconcentrating and hypotensive activities of atrial natriuretic peptide in binephrectomized rats.

In addition to its blood pressure lowering effect, atrial natriuretic peptide (ANP) infusion, increases hematocrit and decreases plasma volume by inducing a transfer of plasma fluid from the vascular to the interstitial compartment. We explored the dose-dependence as well as the reversibility of these actions by measuring changes in mean arterial pressure (MAP), hematocrit and plasma protein concentration (PPC) in anesthetized acutely binephrectomized Sprague-Dawley rats. Infusion of ANP (10, 100 or 1000 ng/kg/min for 45 min) dose-dependently reduced MAP (+2.3 +/- 1.8, -5.8 +/- 2.5 and -8.6 +/- 1.3%) and increased hematocrit (1.7 +/- 0.4, 8.1 +/- 0.4 and 9.0 +/- 0.6%), corresponding to calculated decreases in plasma volume of 3.0 +/- 0.6, 13.1 +/- 0.6 and 14.4 +/- 0.9% respectively. PPC increased significantly less than expected for a plasma volume reduction without proteins extravasation indicating that some loss of plasma proteins occurred in response to ANP. Both the reduction in MAP and plasma volume were reversible within 45 min after discontinuation of ANP infusion. During the recovery period, PPC decreased to values lower than baseline suggesting that the hemodilution was not associated with a detectable return of proteins into the circulation. Thus, in binephrectomized rats, infusion of ANP induced a dose-dependent and reversible reduction in arterial pressure and plasma volume through an extrarenal mechanism. Moreover, ANP dose-dependently increased the vascular permeability to proteins; the escaped proteins remained out of the vascular space for at least the duration of the experiment (ie 45 min post-infusion).

Animals↗
PubMed1994

Blunted effect of ANP on hematocrit and plasma volume in streptozotocin-induced diabetes mellitus in rats.

Atrial natriuretic peptide (ANP) infusion increases hematocrit and decreases plasma volume by inducing a transfer of plasma fluid from the vascular to the interstitial compartment. Diabetes mellitus is associated with resistance to the renal actions of ANP. We explored the possibility that the extrarenal responses to ANP may also be altered in the diabetic state by measuring changes in arterial pressure and hematocrit during infusion of ANP (1 microgram.kg-1 x min-1 for 45 min) into anesthetized, acutely nephrectomized rats 2-3 wk after induction of diabetes from intravenous streptozotocin (STZ) injection (60 mg/kg). Blood glucose was significantly elevated in diabetic rats when compared with control and insulin-treated diabetic rats. Arterial pressure during ANP infusion decreased similarly in control; diabetic, and insulin-treated diabetic rats (by 7.6 +/- 1.6, 9.6 +/- 1.9, and 8.2 +/- 2% respectively; all P < 0.002). In control rats, hematocrit increased progressively to a maximum value of 9.5 +/- 0.9% as a result of the infusion, corresponding to a decrease in plasma volume of 16.3 +/- 1.3%. In contrast, the ANP-induced increase in hematocrit was markedly blunted in diabetic rats (1.6 +/- 0.8%; P < 0.0001 vs. ANP infusion in control rats). Reducing the hyperglycemia in diabetic rats by insulin therapy restored the increase in hematocrit in response to ANP (8.5 +/- 1.1%; P < 0.0001 vs. ANP infusion in diabetic rats and P = NS vs. control rats). ANP infusion increased plasma ANP levels to the same extent in the three groups, whereas plasma guanosine 3',5'-cyclic monophosphate (cGMP) was significantly less in diabetic as compared with control and insulin-treated diabetic rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Effect of dietary sodium chloride on insulin receptor number and mRNA levels in rat kidney.

Insulin has been postulated to play a role in the pathophysiology of essential hypertension via an antinatriuretic action. To further explain the sodium insulin interaction in the kidney, we studied effects of different salt intakes on insulin receptor binding and mRNA levels in tissues from rats maintained on 0.07%, 0.3%, or 7.5% NaCl for 14 days. Scatchard analysis of competition data from in situ autoradiography studies resulted in curvilinear profiles, indicating the presence of either two classes of receptors or a single class of receptors with a negative cooperative hormone-receptor interaction. When data were analyzed using the two-site model, binding capacity of the high-affinity receptor site was significantly less in high-salt-fed rats. No significant differences between dietary groups were observed in apparent dissociation constants of the two receptor sites or in maximal binding capacity of the low-affinity, high-capacity site. Analysis of insulin binding to glomeruli, cortex, outer medulla, and inner medulla indicated that the high-salt diet was associated with decreased receptor density in all regions studied. Insulin receptor mRNA, as quantified by Northern and slot blot analysis, was inversely related to salt intake in absence of a change in plasma glucose, insulin, and corticosterone levels. Both 7.2- and 9.4-kb transcripts were similarly affected by dietary sodium content. Plasma renin concentration and renal renin mRNA levels were decreased but blood pressure was not affected by high-salt diet.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Right atrial myxoma with pulmonary embolism.

Right atrial myxomas are rare tumors that often go undiagnosed. Pulmonary embolism originating from the tumor mass is a potentially fatal complication. We report the case of a young man in whom a right atrial myxoma with recurrent episodes of pulmonary embolism was diagnosed 1 month after the beginning of symptoms by two-dimensional transthoracic and transesophageal echocardiography. Early diagnosis of cardiac myxomas is important since surgical treatment is usually resolutive with low recurrence rates and good long-term survival.

Adult↗
PubMed1994

The cardiac renin-angiotensin system in STZ-induced diabetes.

To determine the effect of diabetes on the cardiac renin-angiotensin system, we compared angiotensin II binding density and renin, angiotensinogen, and type 1 angiotensin II (AT1) receptor mRNA levels in hearts of Sprague-Dawley rats 14 days after the administration of streptozotocin (STZ), in vehicle-treated control rats, and in STZ-administered rats made euglycemic with insulin. Myocardial angiotensin II receptor density, determined using an in situ autoradiographic technique, was increased significantly in hyperglycemic diabetic rats in comparison with control rats and euglycemic diabetic rats (P < 0.01) as a result of an increase in both AT1 and AT2 (type 2 angiotensin II) subtypes. The myocardial AT1 receptor mRNA level, determined by slot blot hybridization, was also significantly greater in the hyperglycemic diabetic rats (P < 0.005). Neither plasma renin concentration nor cardiac renin or angiotensinogen mRNA levels differed among the three study groups. In an additional experiment, control and diabetic rats were infused with angiotensin II (200 ng.kg-1.min-1 i.p. for 7 days) or vehicle. Plasma renin concentration decreased significantly, whereas no significant changes occurred in cardiac renin or angiotensinogen steady-state mRNA levels. As in the first experiment, levels of AT1 receptor mRNA were significantly greater in the diabetic rats. Thus, myocardial angiotensin II receptor density is increased in diabetic rats in association with an increase in steady-state AT1 receptor mRNA levels, an abnormality that appears to be independent of changes in the circulating renin-angiotensin system.

Analysis of Variance↗
PubMed1994

In situ characterization of renal insulin receptors in the rat.

Insulin regulates carbohydrate metabolism, and water, sodium, potassium, and phosphate reabsorption in the kidney by binding to specific receptors. Insulin receptors have been identified in the kidney using membrane preparations obtained from both glomeruli and tubules. In this study, an autoradiographic technique was used to characterize insulin receptors in the rat kidney. Frozen tissue sections were preincubated to remove endogenously bound insulin, incubated in a buffer containing 200 microM 125I-Tyr-insulin, washed, and dried before exposure on Ultrofilm. Binding density was assessed by computerized microdensitometry. In the cortex, binding density was comparable in glomeruli and tubules. In the medulla, bound radioligand was found primarily in longitudinal structures traversing the outer portion, presumably corresponding to vascular bundles, and in the inner portion. Scatchard analysis of competition binding data resulted in curvilinear profiles, indicating either two classes of receptors with different affinity or the presence of a single class of receptors with a negative cooperative hormone-receptor interaction. Data analyzed for a two-site model showed one receptor site with Kd of 0.39 +/- 0.14 nmol/l and Bmax of 3.5 +/- 1.0 x 10(10) receptors/mm3 and another site with Kd of 0.30 +/- 1.1 pmol/l and a Bmax of 3.2 x 10(13) receptors/mm3. Thus, in situ autoradiography can be used to determine distribution and binding characteristics of insulin receptors in rat kidney and might be employed in receptor studies on rat models of human disease.

Animals↗
PubMed1994

[Gene expression of the renin-angiotensin system in compensatory renal hypertrophy secondary to contralateral nephrectomy].

Angiotensin II may act as an angiogenic and growth promoting factor on different cell types. To assess the role of angiotensin II on the compensatory renal response of the remnant kidney to unilateral nephrectomy (UNX), we measured renin, angiotensinogen, and angiotensin II type 1 receptor (AT1) mRNA levels as well as angiotensin II receptor density in 2 groups of 7 Sprague-Dawley rats 7 days after either shamp operation or UNX, Following UNX, the ratio of kidney weight to body weight (KW/BW) increased from 0.38 +/- 0.01 to 0.46 +/- 0.01% (p < 0.01). Neither renin (kidney) or angiotensiongen (kidney and liver) mRNA levels, determined by slot blot hybridization, changed after UNX. Angiotensin II receptor density was determined using an 125I-Sar1-Ile8 Ang II in situ receptor binding assay on fixed kidney sections. Binding specificity was verified using unlabeled Sar1-Ang II. Glomerular angiotensin II receptor density did not change significantly after UNX, nor did AT1 receptor mRNA. Thus, these data do not support a critical role for angiotensin II in the compensatory renal growth following uninephrectomy.

Animals↗
PubMed1994

[Resistance to hemoconcentration but non hypotensive action of atrial natriuretic peptide in diabetes mellitus induced by streptozocin in the rat].

ANP infusion increased hematocrit and decreased plasma volume (PV) by inducing a shift of plasma fluid from the vascular towards the interstitial compartment. Rats with experimental diabetes mellitus resulting from streptozotocin (STZ) treatment exhibit renal resistance to infused ANP. To determine if resistance to the extrarenal actions of ANP also occurs in these conditions, changes in arterial pressure and hematocrit were measured during infusion of ANP (1 microgram/kg/min for 45 min) in anesthetized binephrectomized rats 2-3 weeks after induction of diabetes. Blood glucose was significantly elevated in diabetic when compared to control and insulin-treated diabetic rats. Arterial pressure decreased similarly in control, diabetic and insulin-treated diabetic rats (by 7.6 +/- 1.6, 9.6 +/- 1.9 and 8.2 +/- 2% respectively; all p < 0.0002). In control rats, hematocrit increased progressively to a maximal value of 9.5 +/- 0.9% corresponding to a decrease in PV of 16 +/- 1%. In contrast, the ANP-induced increase in hematocrit was markedly blunted in diabetic rats (1.6 +/- 0.8%; p < 0.0001 vs ANP infusion in control rats), corresponding to a decrease in PV of only 2.2 +/- 1%. In addition, reducing the hyperglycemia in diabetic rats by insulin therapy restored the increase in hematocrit to ANP (8.5 +/- 1.1%; p < 0.0001 and p = NS vs ANP infusion in diabetic and control rats respectively). PV, measured at the end of the infusion period, did not differ between control and insulin-treated diabetic rats infused with ANP (21.3 +/- 1.4 and 22.5 +/- 1.4 ml/kg).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

[Resistance to the action of atrial natriuretic peptide and urodilatin in Heymann nephritis in vitro].

We examined renal sodium handling in rats with Hymann nephritis (HEN), an immunologically mediated model of nephrotic syndrome. Rats were studied 9-14 days following i.p. injection of anti-Fx1A antiserum. We previously demonstrated that HEN had a blunted volume expansion natriuresis (2% body weight isotonic saline infused over 5 min), excreting sodium at only half the rate of normal controls (CTL) despite similar increase in plasma atrial natriuretic peptide (ANP) concentration. Urinary excretion of cGMP accumulation by isolate glomeruli and inner medullary collecting duct (IMCD) cells in response to increasing concentration of ANP, and RNP (also called urodilatin). Results (fmol/mg prot/10 min) are means +/- SEM: [table: see text]. Basal accumulation of cGMP was not different among the groups, HEN rats hd reduced cGMP accumulation in response to ANP, and RNP. In binding studies using 125I-ANP, no difference in either density or affinity was found between CTL and HEN rats. Thus, there is a renal resistance to ANP in rats with HEN, which can be extended to other agents acting through the cGMP pathway. This resistance is not due to impaired binding of ANP, but to impaired accumulation of cGMP in responsive tissues, reflecting perhaps increased cGMP catabolism by phosphodiesterase. Such an observation may account for the altered sodium handling in nephrotic rats.

Animals↗