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

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 (All). To define the role of All in mediating this altered responsiveness, we assessed the effect of a converting enzyme inhibitor (enalapril) on RBF and its responsiveness to All 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 in2) did (P < 0.025). Arterial blood pressure did not change in the modulators with the salt loading, whereas in the nonmodulators, blood pressure rose (P < 0.004).After enalapril administration for 66 h, there was a significant difference (P < 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 All 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 All was also significantly enhanced (P = 0.027) in the nonmodulators, suggesting that enalaprilinduced increase in RBF reflected a fall in intrarenal All levels, and not an increase in prostaglandins or kinins, which would have blunted the renal response to All.Thus, short-term converting enzyme inhibition corrected abnormalities in sodium-mediated modulation of renal vascular responsiveness to All. 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 All, raises the intriguing possibility that converting enzyme inhibition reversed the failure of the renal blood supply to respond to

Prolonged converting enzyme inhibition in non-modulating hypertension.

“…In the kidney, the subnormal renal blood flow in nonmodulating subjects on a high sodium diet and correction after CEI is consistent with the hypothesis that intrarenal concentrations of Ang II are inappropriately elevated in non-modulators. 16 The present study on a sodium-restricted intake is consistent with this hypothesis; basal PAH clearance progressively increased after CEI in hypertensive subjects, but a significant increment above control was only observed in non-modulators at 6 weeks ( Table 2). An alternative explanation could be that, in addition to lowering tissue Ang II levels, CEI may also alter tissue or circulating prostaglandin and bradykinin levels.…”

Atrial natriuretic peptide in non-modulating essential hypertension.

“…Then, an impaired aldosterone response to acute volume depletion was described by Williams et al 2 in a similar subgroup of hypertensive patients. At present, other characteristics of non-modulating hypertension have been described (see References 3 and 4 for review), including an increased blood pressure sensitivity to dietary salt intake 5 and decreased I) renal blood flow response to both angiotensin II (Ang II) and sodium loading, 5 -6 2) aldosterone response to Ang II, 6 3) renin suppression after both Ang IP and saline infusions, 8 and 4) sodium excretion after sodium loading. 9 Because an impaired responsiveness to Ang II of the adrenal gland and kidney seems to determine the hormonal and hemodynamic characteristics of nonmodulators, a tissue refractoriness to Ang II has been suggested as the primum movens of non-modulating hypertension (see References 3 and 4 for review).…”

Evolution of diuretics and ACE inhibitors, their renal and antihypertensive actions‐parallels and contrasts.

“…These individuals have been termed 'non-modulators' and it is in this subset of hypertensives that ACE inhibition is effective both in reversing the failure of renal blood flow to respond to sodium loading and in causing a substantial blood pressure reduction (Redgrave et al, 1985).…”