EFFECT OF ATRIAL-NATRIURETIC-PEPTIDE (8-33-MET ANP) IN PATIENTS WITH HYPERTENSION

In this pilot study we investigated the effects of a 4-h infusion of atrial natriuretic peptide (8-33 Met ANP) on hemodynamic, renal, and hormonal parameters in 12 patients with hypertension. Either 8-33 ANP in 5% manitol (0.7-mu-g/min [eight patients] and 1.05-mu-g/min [four patients]) or placebo (5% manitol) was infused for 4 h on 2 consecutive days in a randomized double-blind crossover design. The plasma levels of ANP were not significantly different between the two doses of ANP and therefore the results from the two doses were combined. Plasma ANP increased from 61 +/- 24 pg/mL to 291 +/- 55 pg/mL after 2 h and to 288 +/- 40 pg/mL after 4 h. ANP caused a significant lowering of systolic blood pressure after 2 h of infusion from 148 +/- 5 mm Hg to 142 +/- 5 mm Hg (P < .05) and to 128 +/- 6 after 4 h (P < .01). Two hours after discontinuation of the infusion, systolic blood pressure was 126 +/- 6 and 135 +/- 7 mm Hg 4 h after the end of the infusion. Diastolic blood pressure did not change. Heart rate increased from 69 +/- 3 beats/min to 74 +/- 3 beats/min after 4 h and to 78 +/- 4 beats/min 2 h after termination of the infusion. Cardiac output did not change significantly. Urinary sodium and chloride increased significantly but creatinine clearance did not change. Plasma aldosterone decreased after 2 h of ANP infusion from 9.8 +/- 1.7 ng/dL to 6.7 +/- 0.9 ng/dL (P < .01) and to 6.5 +/- 1.2 ng/dL after 4 h (P < .05). Plasma renin activity decreased from 0.81 +/- 0.1 ng angiotensin I/ml/h to 0.57 +/- 0.1 after 2 h of infusion (P <.05). There were no significant changes in plasma catecholamines or arginine vasopressin. Two patients developed severe hypotension and bradycardia and one of them had a sinus pause of 7.4 sec associated with loss of consciousness. Neither of these two patients had a significant increase in plasma catecholamines in response to the severe hypotension, suggesting that ANP may have inhibited their sympathetic response and increased their sensitivity to vagal cardioinhibitory reflexes. In conclusion, infusion of ANP in hypertensive patients causes prolonged lowering of systolic blood pressure with no change in diastolic pressure and cardiac output. Also, ANP infusion causes natriuresis and suppression of renin and aldosterone. However, in some patients ANP infusion may cause severe hypotension and bradycardia probably as a result of a sympathoinhibitory action of ANP associated with an increased sensitivity to vagal cardioinhibitory reflexes.