ABNORMAL ATRIAL-NATRIURETIC-PEPTIDE AND RENAL RESPONSES TO SALINE INFUSION IN NONMODULATING ESSENTIAL HYPERTENSIVE PATIENTS

Background Nonmodulation seems to represent an inheritable trait chara cterized by abnormal angiotensin-mediated control of aldosterone relea se and renal blood supply and salt-sensitive hypertension. Recently, w e demonstrated that atrial natriuretic peptide (ANP) response to angio tensin II also is altered in nonmodulators. Moreover, an abnormal ANP response to acute volume expansion has been shown by others in hyperte nsive patients displaying some features of nonmodulators. These data i nduced us to hypothesize that nonmodulation could be characterized by an abnormal ANP response to saline load. Methods and Results Forty-thr ee essential hypertensive men were subdivided into low-renin patients (n=12), nonmodulators (n=15), and modulators (n=16) according to their renin profile and ability to modulate aldosterone and p-aminohippurat e clearance responses to a graded angiotensin II infusion (1.0 ng.kg(- 1) min(-1) and 3.0 ng kg(-1) min(-1) for 30 minutes each) on both a lo w- (10 mmol Na+ per day) and a high- (210 mmol Na+ per day) Na+ intake . The intravenous saline load (0.25 mL.kg(-1) min(-1) for 2 hours) per formed on a low-Na+ diet increased plasma ANP levels in low-renin (fro m 14.30+/-4.68 to 23.30+/-7.52 fmol/mL at 120 minutes, P<.05) and modu lating patients (from 10.95+/-3.55 to 18.21+/-5.42 fmol/mL at 120 minu tes, P<.05), whereas it did not change the hormone levels in nonmodula tors (from 10.77+/-3.25 to 13.83+/-5.70 fmol/mL at 120 minutes, P=NS). When patients switched from a low- to a high-NaCl diet, plasma ANP le vels increased significantly in all groups. However, when the saline l oad was repeated on a high-NaCl intake, ANP levels increased in both l ow-renin and modulating patients (P<.05), whereas it failed to increas e in nonmodulators. Conclusions Nonmodulating hypertensive patients sh owed a reduced ANP response to saline infusion in the presence of a no rmal increase of plasma ANP with dietary NaCl load. The impaired ANP r esponse to saline infusion could be due to a different distribution of volume load and contribute to determining the reduced ability to excr ete sodium that is commonly described in nonmodulators.