Converting enzyme inhibition prevents the effects of atrial natriuretic factor on baroreflex responses in humans

The aim of this study was to assess the influence of atrial natriuretic factor (ANF) on arterial baroreflex chronotropic responses and to investigate whether this effect of ANF is affected by angiotensin converting enzyme inhibition (CEI). For this purpose, in 13 normal volunteers, the reflex chronotropic responses to arterial baroreceptor stimulation (phenylephrine, 25-100 μg i.v.) or deactivation (nitroglycerin, 25-100 μg i.v.) were evaluated in control conditions and during the steady-state phase of a sustained infusion of ANF (50 ng/kg/min) or placebo, before and during prolonged treatment with the converting enzyme inhibitor enalapril (20 mg p.o. for 5 days). ANF infusion, which raised plasma ANF levels from 48±19 to 1,765±203 pg/ml, was associated with a slight decrease in systemic blood pressure and no change in heart rate. In addition, it caused a significant increase of the regression slope obtained with phenylephrine (from 11.3±2 to 18.5±2 msec/mm Hg) and a significant reduction of slope of the nitroglycerin-produced regression line (from 9.3±1 to 5.6±0.6 msec/mm Hg). After sustained CEI, which raised plasma renin activity from 1.4±0.4 to 19.9±5 ng/ml/hr, ANF infusion induced an increase in plasma ANF levels and a reduction in blood pressure comparable to those observed in control conditions. During CEI, however, ANF infusion had no significant effect on the chronotropic baroreflex responses produced by phenylephrine or nitroglycerin. Chronotropic and pressor responses to cold exposure were unchanged after CEI and during ANF. Our results demonstrate that ANF, at this dosage, significantly modulates the chronotropic responses to baroreceptor manipulation so that bradycardic responses are enhanced and tachycardic responses blunted. They also show that CEI prevents this effect of ANF. Although other possibilities cannot be excluded, the interaction of atrial peptide with the baroreflex mechanisms may be accounted for by antagonism of the effects of angiotensin II on baroreflex pathways.