Enalapril and pressure-diuresis in hypertensive rats transgenic for mouse renin gene.
The recent development of a transgenic rat strain bearing the mouse ren-2 renin gene [TGR(mRen2)27] has provided a new monogenetic model of hypertension. Other hypertensive rat strains are characterized by a blunted pressure-diuresis-natriuresis response such that higher renal perfusion pressures are required to excrete normal amounts of water and sodium. Dysfunction of the renin-angiotensin and nitric oxide systems may cause in this abnormality. This study examined the effect of enalapril on the pressure-natriuresis response and urinary nitric oxide metabolite excretion in 6-month-old TGR(mRen2)27 rats. The slope of the line relating renal perfusion pressure and urine flow rate in TGR (0.08+/-0.01 microl x min(-1) x g kidney weight(-1) mm Hg[-1]) was significantly lower than that in control rats (0.15+/-0.01 microl x min(-1) x g kidney weight(-1) mm Hg[-1]). Pressure-natriuresis responses were also shifted to higher pressure levels in TGR. Treatment with enalapril for 3 months lowered the mean arterial pressure from 94+/-2 to 84+/-4 mm Hg in control rats and from 146+/-3 to 89+/-3 mm Hg in TGR. The slopes of lines relating renal perfusion pressure and urine flow rate as well as sodium excretion were significantly increased by enalapril in control and transgenic animals. Urinary nitric oxide metabolite excretion rose similarly with increasing renal perfusion pressure in both control and TGR rats and was not affected by enalapril. These results confirm that older TGR rats have a blunted pressure-diuresis-natriuresis response that can be corrected by inhibition of the renin-angiotensin system and suggest that their production of nitric oxide is normal.
Springate
J
J
Department of Pediatrics, School of Medicine and Biomedical Sciences, State University of New York at Buffalo, USA.
Van Liew
J
J
Ganten
D
D
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D000818:Animals; D030801:Animals, Genetically Modified; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D004231:Diuresis / Q000187:drug effects*; D004656:Enalapril / Q000627:therapeutic use*; D006973:Hypertension / Q000188:drug therapy* / Q000235:genetics; D008297:Male; D051379:Mice; D009318:Natriuresis / Q000187:drug effects; D009566:Nitrates / Q000652:urine; D009573:Nitrites / Q000652:urine; D051381:Rats; D017207:Rats, Sprague-Dawley; D012079:Renal Circulation / Q000187:drug effects; D012083:Renin / Q000235:genetics*
D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D009566:Nitrates; D009573:Nitrites; D004656:Enalapril; D012083:Renin