The Importance of the Renin-Angiotensin System in the Development and Maintenance of Hypertension in the Two-Kidney One-Clip Hypertensive Rat

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Abstract
Blood pressure, renin concentration and angiotensin [A] II were measured in unanesthetized 2-kidney 1-clip hypertensive rats at 1 and 2 days, at weekly intervals up to 10 wk and at 15 and 20 wk after clipping. Compared with values in sham-operated rats, renin and AII were initially increased at 1-2 days but were then suppressed between 2-4 wk to levels similar to that found in sham-operated rats. Between 5-20 wk, renin and AII increased again to high levels. There was a significant correlation between AII and blood pressure in acute rats 1-2 days after clipping (P < 0.05) and in chronic rats 8-20 wk after clipping (P < 0.001). There was no difference in the slope of the regression lines, but the regression line for the chronic rats was shifted upwards in a parallel manner. The acute hypotensive response (-20.3 .+-. 24.9 mm Hg SD) in 26 chronic rats given converting enzyme inhibitor was related to the basal renin and AII levels and followed the slope of the AII/blood pressure regression line for all chronic rats. Only 1 of 26 rats reduced its blood pressure to normal levels. In 12 rats at 4 wk after clipping, when blood pressure was elevated, but AII was suppressed, there was only a small fall in blood pressure (-7.1 .+-. 7.2 mm Hg SD). This also followed the AII/blood pressure regression line for chronic rats, but at the lower end. Blood pressure again was not reduced to normal. Apparently, renin and AII are increased up to 20 wk after clipping, there is no change in the net vascular responsiveness to endogenous AII at any stage in this experimental model, and the acute effect of AII is determined solely by its position in the same dose-response curve. Also, with the exception of 1-2 days immediately after clipping, the acute effect of AII plays only a minor, though variable, role in the hypertension, and some other mechanism, as yet undetermined, is of greater importance and begins to have an effect as early as 2 wk after clipping.