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. 1985 Apr;75(4):1285–1290. doi: 10.1172/JCI111828

Correction of abnormal renal blood flow response to angiotensin II by converting enzyme inhibition in essential hypertensives.

J Redgrave 1, S Rabinowe 1, N K Hollenberg 1, G H Williams 1
PMCID: PMC425457  PMID: 2985655

Abstract

In 40-50% of patients with essential hypertension, a high sodium intake does not increase renal blood flow (RBF). These patients have been defined as nonmodulators because sodium intake does not modulate renal and adrenal responsiveness to angiotensin II (AII). To define the role of AII in mediating this altered responsiveness, we assessed the effect of a converting enzyme inhibitor (enalapril) on RBF and its responsiveness to AII in 25 patients with essential hypertension--10 modulators and 15 nonmodulators--and 9 normotensive controls. After 5 d of a 200-meq sodium intake, the nonmodulators did not increase RBF, whereas the normotensives (79 +/- 28 ml/min per 1.73 m2) and modulators (75 +/- 26 ml/min per 1.73 m2) did (P less than 0.025). Arterial blood pressure did not change in the modulators with the salt loading, whereas in the nonmodulators, blood pressure rose (P less than 0.004). After enalapril administration for 66 h, there was a significant difference (P less than 0.01, Fisher Exact Test) in the blood pressure response in the two hypertensive subgroups. In the modulators, there was no change; in the nonmodulators, despite the high salt diet, a blood pressure reduction occurred. In parallel, basal RBF and RBF responsiveness to AII were not changed after converting enzyme inhibition in the normotensive control (n = 9) or the hypertensive modulators (n = 10). Conversely, in the nonmodulators (n = 14), the basal RBF increased significantly (83 +/- 25 ml/min per 1.73 m2; P = 0.01), the increment being indistinguishable from the response to salt loading in normal subjects. Furthermore, renovascular responsiveness to infused AII was also significantly enhanced (P = 0.027) in the nonmodulators, suggesting that enalapril-induced increase in RBF reflected a fall in intrarenal AII levels, and not an increase in prostaglandins or kinins, which would have blunted the renal response to AII. Thus, short-term converting enzyme inhibition corrected abnormalities in sodium-mediated modulation of renal vascular responsiveness to AII. The close quantitative relation of the increase in RBF with sodium loading in normal subjects and modulators, and with converting enzyme inhibition in nonmodulators, viewed in the context of the effectiveness of enalapril only in the latter, and parallel shifts in sensitivity to AII, raises the intriguing possibility that converting enzyme inhibition reversed the failure of the renal blood supply to respond to sodium loading. Thus, converting enzyme inhibitors may reduce blood pressure specifically in this subset of patients with essential hypertension, who are sodium sensitive by way of mechanisms more closely related to local than systemic activity of the renin-angiotensin system.

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Selected References

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