Are non-modulating patients with essential hypertension a distinct subgroup? Implications for therapy.

In 40 to 50 percent of the essential hypertensive population, a high intake of sodium does not increase renal blood flow. These patients have been called "non-modulators" since their adrenal and renal vascular responses to angiotensin II are not modified by changes in sodium intake. To determine if these patients form a distinct subgroup, the frequency distribution of four characteristics that have been reported to be abnormal in non-modulators were analyzed: aldosterone secretory response to acute volume depletion, plasma aldosterone response to angiotensin II infusion, plasma renin activity response to saline infusion, and renal blood flow response to salt loading. All four characteristics had a bimodal distribution in patients with hypertension. The effect of angiotensin converting enzyme inhibition on two of these abnormalities was also reviewed. In both cases--aldosterone secretory response to angiotensin II and renal blood flow response to salt loading--converting enzyme inhibition restored the abnormal responses towards normal values in non-modulators without altering the responses in normotensives or modulators. Indeed, the correction of the abnormal renal blood flow response to salt loading through converting enzyme inhibition may explain how converting enzyme inhibitors normalize blood pressure in 50 percent of the patients in whom the renin-angiotensin system is suppressed by an unrestricted, typically high, intake of salt. In summary, non-modulators are a distinct subset of the hypertensive population. Converting enzyme inhibition corrects the abnormalities that may be responsible for their hypertensive condition and, therefore, may be a specific form of therapy for these patients.