Hypertensive dysregulation and its modification by calcium channel blockade in nonoliguric renal failure

To investigate the pathogenetic constellation and its modification by calcium channel blockade in hypertension associated with chronic nonoliguric renal failure, blood pressure (BP), various pressor factors or correlates, cardiovascular responsiveness, and plasma atrial natriuretic peptide (ANP) were assessed in 15 hypertensive patients (serum creatinine 160-715 mumol/l) before and after 6 weeks of intervention with the agent nitrendipine. On placebo, these patients had a lower plasma angiotensin II (AngII) clearance and higher values of supine plasma AngII, aldosterone, norepinephrine (NE), and heart rate than healthy humans. Acute responses of BP to AngII and of heart rate to isoproterenol were blunted in the patients (p less than 0.05-0.001). Plasma ANP was elevated, correlated positively with systolic BP, and rose in response to NE pressor infusion (p less than 0.05-0.001). Exchangeable sodium and blood volume did not differ significantly from normal values. Nitrendipine reduced the cardiovascular responses to AngII, NE, and isoproterenol and lowered supine BP from 173/102 +/- 5/2 to 146/81 +/- 3/3 mm Hg and upright BP from 170/105 +/- 5/2 to 145/86 +/- 4/3 mm Hg (p less than 0.05-0.001); except for slightly increased plasma AngII, the levels of other endocrine variables, exchangeable sodium, blood volume, and creatinine clearance were not significantly modified.

Hypertension accompanying chronic nonoliguric renal impairment seems to be strongly AngII and probably also NE dependent. Circulating ANP levels are high in this setting. Calcium channel blockade with nitrendipine effectively reduces cardiovascular AngII and NE dependence and BP.