Angiotensin II subtype AT1 receptor blockade prevents hypertension and renal insufficiency induced by chronic NO-synthase inhibition in rats.

Aim of the present study was to investigate the influence of the angiotensin II (ANG II) subtype 1 (AT(1)) receptor blockers fonsartan and losartan on blood pressure, cardiac -dynamics and -metabolism as well as functional and morphological changes in the kidney of rats after long-term inhibition of the nitric oxide (NO) synthase by N(G)-nitro-L-arginine methyl ester (L-NAME). Oral chronic treatment with L-NAME in a dose of 25 mg/kg/d over 6 weeks caused a significant increase in systolic blood pressure (198+/-13 mmHg) when compared to untreated rats (144+/-4 mmHg). Animals receiving simultaneously L-NAME and fonsartan (10 mg/kg/d) or losartan (30 mg/kg/d) were protected against blood pressure increase.

S3226, a novel NHE3 inhibitor, attenuates ischemia-induced acute renal failure in rats.

Background: Acute renal failure (ARF) remains a major problem in clinical nephrology characterized by sudden loss of the kidney function due to ischemia, trauma, and/or nephrotoxic drugs. The current therapy of ARF is symptomatic with mortality rates exceeding 50%. The aim of this study was to investigate the effects of an intravenous infusion of S3226 (3-[2-(3-guanidino-2-methyl-3-oxopropenyl)-5-methyl-phenyl]-N-isopropylidene-2-methyl-acrylamide dihydrochloride), a selective Na+/H+ exchange subtype 3 (NHE3) blocker, in ischemia-induced ARF in rats.

Role of NHE isoforms in mediating bicarbonate reabsorption along the nephron.

This study assessed the functional role of Na(+)/H(+) exchanger (NHE) isoforms NHE3 and NHE2 in the proximal tubule, loop of Henle, and distal convoluted tubule of the rat kidney by comparing sensitivity of transport to inhibition by Hoe-694 (an agent known to inhibit NHE2 but not NHE3) and S-3226 (an agent with much higher affinity for NHE3 than NHE2). Rates of transport of fluid (J(v)) and HCO(3)(-) (J(HCO3)) were studied by in situ microperfusion. In the proximal tubule, addition of ethylisopropylamiloride or S-3226 significantly reduced J(v) and J(HCO3), but addition of Hoe-694 caused no significant inhibition.

Role of Na(+)/H(+) exchanger NHE3 in nephron function: micropuncture studies with S3226, an inhibitor of NHE3.

Na(+)/H(+) exchanger NHE3 is expressed in the luminal membrane of proximal tubule and thin and thick ascending limb of Henle's loop. To further define its role, the novel NHE3 inhibitor S3226 was employed in micropuncture experiments in nephrons with superficial glomeruli of anesthetized rats. Microperfusion of proximal convoluted tubule with S3226 revealed a dose-dependent inhibition of reabsorption (IC(50) of 4-5 microM) with a maximum inhibition of 30% for fluid and Na(+).

[Animal experiment models of hypertension in pregnancy--an alternative to clinical studies?].

Unlabelled: Because of ethical constraints upon research during human pregnancy and of the heterogeneity of preeclampsia a number of experimental animal models were used to study pathophysiology of preeclampsia. We reduced the uteroplacental flow by aortic clip technique in 72 SHR-rats in 4 groups (G 1 not gravid--no clip, G 2 not gravid--aortic clip, G 3 gravid--no clip, G 4 gravid--aortic clip). While gravidity normalised blood pressure in SHR (G 3), reduction of the uteroplacental flow significantly increased maternal blood pressure (G1 240/180 mmHG, G2 238/183 mmHg, G3 148/99 mmHG, G4 200/145 mmHg) and leads to significant higher hematocrit, significant lower plasma renin activity and aldosterone plasma concentration, as it is found in human superimposed preeclampsia.