title: Renal effects of captopril and nitrendipine in transgenic rats with an extra renin gene.
abstract: We investigated the acute effects of captopril and nitrendipine on renal function and sodium excretion in hypertensive, male, heterozygous transgenic rats harboring a mouse renin gene [TGR (mRen-2)27]. Both drugs reduced blood pressure dose dependently in conscious transgenic rats. The oral ED20 for captopril was 0.5 mg/kg and 2.7 mg/kg for nitrendipine. In orally salt-loaded (20 mL/kg saline) transgenic rats captopril (0.3 to 3.0 mg/kg) reduced sodium excretion by approximately 90% in the 6 hours after administration, whereas equally antihypertensive doses of nitrendipine increased sodium excretion by approximately 100%. The antinatriuretic effect of captopril was accompanied by a reduction in creatinine clearance and a decrease in the excretion of cyclic GMP. In orally water-loaded (20 mL/kg water) transgenic rats captopril also reduced sodium excretion by more than 90%, and nitrendipine slightly increased sodium excretion. In control Sprague-Dawley rats the effects were opposite; namely, captopril tended to increase natriuresis, and nitrendipine caused a small but distinct decrease in sodium excretion. Intravenous captopril in anesthetized transgenic rats caused an antinatriuresis with a decrease in inulin clearance but not in Sprague-Dawley rats. To control for non-renin-related effects of captopril, we gave transgenic rats oral losartan. Losartan also decreased urinary sodium excretion. The results suggest a role for the renin-angiotensin system in the maintenance of glomerular filtration rate and sodium excretion in transgenic TGR (mRen-2)27 rats.
authors.affiliation: Institut für Herzkreislauf-und Arterioskleroseforschung, Bayer AG, Wuppertal, FRG.
authors.forename: C
authors.initials: C
authors.lastname: Hirth-Dietrich
authors.forename: J P
authors.initials: JP
authors.lastname: Stasch
authors.forename: D
authors.initials: D
authors.lastname: Ganten
authors.forename: F C
authors.initials: FC
authors.lastname: Luft
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D009320:Atrial Natriuretic Factor / Q000494:pharmacology; D002216:Captopril / Q000494:pharmacology*; D006152:Cyclic GMP / Q000096:biosynthesis; D007668:Kidney / Q000187:drug effects*; D008297:Male; D009568:Nitrendipine / Q000494:pharmacology*; D011188:Potassium / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012083:Renin / Q000235:genetics* / Q000502:physiology; D012964:Sodium / Q000378:metabolism
chemical_list: D009320:Atrial Natriuretic Factor; D009568:Nitrendipine; D002216:Captopril; D012964:Sodium; D012083:Renin; D006152:Cyclic GMP; D011188:Potassium