Reversal of two-kidney one clip renovascular hypertension in the rat.

Abstract

SUMMARY Attempted correction of two-kidney, one clip Goldblatt hypertension in the rat was carried out by three techniques: removal of the constricting dip, removal of the Iscberaic kidney, and converting enzyme blockade by oral captopril. Since duration of hypertension is said to be a critical factor, groups of rats were studied after short term (< 6 weeks from clipping) and chronic (> 4 months) hypertension. Blood pressure, sodium balance, and plasma renin concentration (PRC) were followed before and after these correcting procedures. In a control group of animals, removal of a loose renal artery clip did not Influence blood pressure and only caused trivial postoperative retention of sodium. Undipptng, however, normalized blood pressure in both short-term and chronic hypertension. After a major postoperative fall, blood pressure returned to somewhat elevated levels after nephrectomy in animals with chronic (but not short-term) hypertension. Sodium balance became markedly positive with the fall in blood pressure of operated hypertensive anlmpu and was significantly correlated with the fall in blood pressure in these four groups at 7 days (r = 0.43). Captopril also produced a fall in blood pressure at 24 hours, with a positive sodium balance, although the relationship between blood pressure fall and sodium balance did not reach statistical significance (r = 0 JO). The PRC was elevated in all hypertensive groups, although individual values overlapped with values from normal rats and nonhypertensive rats with a loose renal artery dip. The PRC fell to normal or subnormal values after either operative procedure and stabilized for at least 2 months Independently of whether blood pressure fell or not. It is concluded that neither sodium retention nor renin hypersecretion maintains blood pressure In this model. Also, the rapidity of the blood pressure fall is not consistent with a role for vascular hypertrophy. Tbe greater efficacy of unclipping suggests that the revascularized kidney after this procedure exerts a vasodepressor function independent of sodium excretion or the renin-angiotensin system. T HE mechanism by which sustained blood pressure elevation follows renal artery constriction is still uncertain. Attention has been focused on three factors: the renin-angiotensin system, sodium retention, and resistance vessel hypertrophy.

Effects of Restoration of Blood Flow on the Development of Aortic Atherosclerosis in ApoE −/− Mice With Unilateral Renal Artery Stenosis

“…Ang‐II levels were decreased in the revascularization groups after ligature removal (when measured at 15 days) and remained suppressed for the duration of the experiment. These results are similar to studies in the rat two‐kidney‐one‐clip (2K1C) model, in which plasma renin concentrations were only 64% of baseline levels when measured 60 days after restoration of renal blood flow 14, 15…”

“…In that model, unilateral renal artery clipping was associated with a marked increase in plasma renin concentration when measured 30.9±1.3 days later (638% of baseline). Removal of the clip resulted in a marked decrease in plasma renin concentration to 82% of baseline at 7 days and 64% of baseline at 60 days 14, 15. Plasma renin levels in 2K1C hypertensive rats declined to levels below those of sham controls in as little as 3 hours after unclipping 35…”

“…Past studies in the rat14, 15 have shown that blood pressure normalizes and plasma renin activity decreases after unclipping either 6 weeks or 4 months after unilateral RAS, but effects on vascular pathology have not been studied. Thus, the purpose of the present study was to examine the effects of transient periods of partial unilateral renal artery constriction on aortic atherogenesis in apolipoprotein E–deficient (ApoE −/− ) mice.…”

Angiotensin II-noradrenergic interactions in renovascular hypertensive rats.

“…Further, the maintenance of an elevated arterial blood pressure in 2-kidney-I-clip Goldblatt rats depends on the renin-angiotensin system for some time after induction of hypertension. Thus, for several weeks after the onset of hypertension, plasma renin activity remains elevated (1) and arterial blood pressure can be normalized by angiotensin II antagonists (4,5), converting enzyme inhibitors (6,7), removal of the ischemic kidney (8), and restoration of renal artery patency (8). As the ravages of hypertension take a toll on the contralateral kidney (9), however, the importance ofthe renin-angiotensin system in sustaining the hypertension becomes less clear.…”

“…As the ravages of hypertension take a toll on the contralateral kidney (9), however, the importance ofthe renin-angiotensin system in sustaining the hypertension becomes less clear. Several months into the hypertensive process, plasma renin activity normalizes (1), and angiotensin H antagonists (4,5) or removal of the ischemic kidney (8,10) no longer reverses the hypertension. Considered together, the current body ofevidence strongly supports a primary role for the renin-angiotensin system in the development and early maintenance of2-kidney-I-clip hypertension, with the importance of the renin-angiotensin system gradually waning with time.…”