ENALAPRIL AND PRESSURE-DIURESIS IN HYPERTENSIVE RATS TRANSGENIC FOR MOUSE RENIN GENE

The recent development of a transgenic rat strain bearing the mouse re n-2 renin gene [TGR(mRen2)27] has provided a new monogenetic model of hypertension. Other hypertensive rat strains are characterized by a bl unted pressure-diuresis-natriuresis response such that higher renal pe rfusion 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 enala pril on the pressure-natriuresis response and urinary nitric oxide met abolite excretion in 6-month-old TGR(mRen2)27 rats. The slope of the l ine relating renal perfusion pressure and urine flow rate in TGR (0.08 +/-0.01 mu l . min(-1) . g kidney weight(-1) . mm Hg-1) was significa ntly lower than that in control fats (0.15 +/- 0.01 mu l . min(-1) . g kidney weight(-1) . mm Hg-1). Pressure-natriuresis responses were als o shifted to higher pressure levels in TGR. Treatment with enalapril f or 3 months lowered the mean arterial pressure from 94+/-2 to 84+/-4 m m Hg in control rats and from 146+/-3 to 89+/-3 mm Hg in TGR. The slop es of lines relating renal perfusion pressure and urine flow rate as w ell as sodium excretion were significantly increased by enalapril in c ontrol and transgenic animals. Urinary nitric oxide metabolite excreti on rose similarly with increasing renal perfusion pressure in both con trol and TGR rats and was not affected by enalapril. These results con firm 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.