ENHANCED SLOW PRESSER EFFECT OF ANGIOTENSIN-II IN 2-KIDNEY, ONE-CLIP RATS

Phase II of two-kidney, one clip (2K1C) Goldblatt hypertension in the rat is characterized by elevated blood pressure and near-normal plasma concentrations of angiotensin II (Ang II) but is reversed by inhibiti on of the renin-angiotensin system. We hypothesized that this angioten sin dependence is due to enhanced responsiveness to the slow presser e ffect of Ang II caused by renal artery stenosis. To test this idea, we submitted rats to either renal artery clipping or sham operation. The se groups were immediately subdivided; some animals received enalapril in their drinking water (508 mu mol/L), and the rest drank distilled water only. After 10 to 14 days, catheters were inserted into the aort a and vena cava, and the rats were housed in metabolism cages. After 3 control days of measurement of mean arterial pressure and other varia bles, the enalapril-treated groups received an intravenous infusion of Ang II at a dose of 3.8 pmol/min (4 ng/min) for 14 days. Rats not dri nking enalapril received only saline vehicle (2 mmol Na+ per day). Aft er 3 days of Ang II infusion, the enalapril-treated 2K1C rats had atta ined a significantly higher level of mean arterial pressure than the e nalapril-treated sham rats. At the end of the Ang II infusion, mean ar terial pressure in enalapril-treated 2K1C rats was 151+/-6 mm Hg versu s 107+/-7 mm Hg in enalapril-treated sham rats. Mean arterial pressure in the enalapril-treated sham rats after Ang II infusion was not sign ificantly different from that of untreated sham rats (109+/-2 mm Hg). No significant differences in urinary sodium excretion or water balanc e were noted between the 2K1C and sham rats. These results support the hypothesis that 2K1C rats exhibit enhanced responsiveness to the slow presser effect of Ang II.