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DOSE-DEPENDENCE AND REVERSIBILITY OF THE HEMOCONCENTRATING AND HYPOTENSIVE ACTIVITIES OF ATRIAL-NATRIURETIC-PEPTIDE IN BINEPHRECTOMIZED RATS
No full textIn 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)
INFLUENCE OF ANGIOTENSIN CONVERTING-ENZYME INHIBITION ON THE PROEDEMATOUS ACTIVITY OF NICARDIPINE
No full textRATS WITH STREPTOZOTOCIN DIABETES-MELLITUS ARE RESISTANT TO THE ACTION OF ATRIAL-NATRIURETIC-PEPTIDE TO INCREASE VASCULAR-PERMEABILITY
No full textANP 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 (I mug/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 < 0.002). 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 contol and insulin-treated diabetic rats infused with ANP (21.3 +/- 1.4 and 22.5 +/- 1.4 ml/kg). In contrast, PV was significantly higher in diabetes (32 +/- 1.1 ml/kg) as compared to both ANP or vehicle (25.2 +/- 1.1 ml/kg) infused control rats. This study demonstrate that a) the effect of ANP on hematocrit and volemia is blunted in STZ-induced diabetes while it's hypotensive action is preserved, and b) restoring the glucose levels to normal in diabetic rats by insulin treatment normalizes the hemoconcentrating effect to exogenous administered ANT. Such an effect may account for the plasma volume expansion observed in untreated diabetic rats
BLUNTED EFFECT OF ANP ON HEMATOCRIT AND PLASMA-VOLUME IN STREPTOZOTOCIN-INDUCED DIABETES-MELLITUS IN RATS
No full textAtrial 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 mu g.kg(-1).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. Acute reduction of hyperglycemia did not restore the ANP-induced increase in hematocrit (1.3 +/- 2.2%; P = NS vs. ANP infusion in diabetic rats). This study demonstrates that 1) the effect of ANP on hematocrit and fluid distribution is blunted in STZ-induced diabetes, while its hypotensive action is preserved, and 2) restoring the glucose levels to normal in diabetic rats by chronic but not by acute insulin treatment normalizes the hemoconcentrating effect of exogenously administered ANP. Such a defect is reflected in a blunted plasma cGMP concentration after ANP infusion in STZ-diabetic rats and may contribute to the altered body fluid physiology in this condition
ATRIAL-NATRIURETIC-PEPTIDE AND BLUNTED RENAL RESPONSES TO VOLUME EXPANSION IN RATS WITH HEYMANN NEPHRITIS
No full textRATS WITH HEYMANN NEPHRITIS ARE RESISTANT TO THE ACTIONS OF ATRIAL AND RENAL NATRIURETIC PEPTIDES TO INCREASE CGMP ACCUMULATION IN-VITRO
No full textWe examined renal sodium handling in rats with Heymann nephritis (HEN), an immunologically mediated model of nephrotic syndrome. Rats were studied 9-14 days following ip 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 was also reduced by half in HEN compared to CTL. We next compared cGMP accumulation by isolated 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 : [GRAPHICS] significantly less than CTL; p < 0.05. 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 I-125-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 perharps increased cGMP catabolism by phosphodiesterase. Such an observation may account for the altered sodium handling in nephrotic rats
AUTORADIOGRAPHIC CHARACTERIZATION OF ANGIOTENSIN-II RECEPTOR SUBTYPES IN RAT INTESTINE
No full textAngiotensin II is known to regulate motility and ion an water absorption in the intestine. These effects are presumed to be mediated by angiotensin II (ANG II) receptors that are present in both mucosal and muscular layers throughout the intestine. To evaluate tissue density and distribution of ANG II receptor subtypes (AT1 and AT2), we performed an in situ autoradiographic study on jejunum, ileum, and colon of Sprague-Dawley rats. Tissue sections (10 mum) were incubated with 500 pM I-125-[Sar1,Ile8]ANG II, fixed with paraformaldehyde vapors, and coated with photographic emulsion. Binding specificity was verified by competition with unlabeled [Sar1]ANG II (10 muM). AT1 and AT2 receptor distribution was characterized by competition with the nonpeptide antagonists losartan (10 muM) and PD123177 (10 muM), respectively, and the density of receptors was quantified by counting the silver grains overlying the different layers of intestinal wall. Specific binding was moderately abundant in the mucosa and the muscularis of both jejunum and ileum, whereas no binding was present in the submucosa and the serosa. Losartan inhibited 86% of radioligand binding to the mucosa in both jejunum and ileum, whereas PD123177 inhibited only 10%. The combination of the two compounds inhibited 96% of specific binding. In the colon, binding was significantly more abundant in the muscularis than in the mucosa. In this segment, losartan inhibited 90% and PD123177 16% of specific binding to muscularis. The combination of these compounds reduced binding by 97%. Thus the predominant ANG II receptor in all intestinal segments is AT1, but a small population of AT2 receptors also seems to be present. Neither intraperitoneal infusion of ANG II (200 ng.kg-1.min-1) for 7 days nor treatment with an angiotensin-converting enzyme inhibitor (enalapril, 3.75 mg.kg-1.day-1 for 10 days) caused a significant change in ANG II receptor density in jejunum, ileum, or colon, indicating that these receptors are not regulated by plasma ANG II levels
Renin, angiotenisnogen, and angiotensin II type I receptor mRNA levels after unilateral nephrectomy
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