Cardiovascular and hormonal responses to ANP infusion in the guinea-pig: effects of angiotensin-converting enzyme inhibition with perindopril.

In the guinea-pig, perindopril inhibited plasma angiotensin converting enzyme (ACE) by 90% when given orally at 2 mg/kg/day during 10 days. Mean blood pressure and plasma aldosterone, cortisol and vasopressin concentrations were not modified by this treatment, while plasma renin activity (PRA) and plasma angiotensin I concentrations increased significantly. The same parameters were studied using a constant intravenous 30 min-infusion of atrial natriuretic peptide (ANP) (0.1 micrograms.kg-1min-1). This dose of ANP infused to anesthetized guinea-pigs induced a significant decrease in mean blood pressure (about -20%) in control and in perindopril treated animals. In ANP infused animals, plasma aldosterone and cortisol concentrations decreased similarly in both groups by about -50%, whereas plasma vasopressin concentrations increased in controls (+169%) but not in perindopril treated guinea-pigs. An increase in PRA and plasma angiotensin I concentrations was observed in both groups after the infusion of ANP. Thus, when ANP demonstrated an potent hypotensive effect a concomitant increase in PRA occurred. The rise observed in vasopressin concentration in control animals was probably mediated by angiotensin II. The fall in plasma aldosterone and cortisol concentrations observed after ANP infusion demonstrated a direct potent action of ANP at the adrenal levels.