ANGIOTENSIN-CONVERTING ENZYME-INHIBITION IMPROVES BAROREFLEX-INDUCED NORADRENALINE SPILLOVER RESPONSES IN RABBITS WITH HEART-FAILURE

Impaired baroreflex function is a characteristic feature of congestive heart failure (CHF), although the mechanism is obscure. This study ex amined the hypothesis that activation of the renin-angiotensin system contributes to baroreflex dysfunction in CHF. The acute effects of an angiotensin converting enzyme inhibitor, enalaprilat, on baroreflex-me diated changes in heart rate (HR), total and renal noradrenaline (NA) spillover rates were examined in conscious rabbits with doxorubicin-in duced cardiomyopathic CHF. Studies were performed under resting condit ions and in response to changes in mean arterial pressure (MAP) induce d by sodium nitroprusside and phenylephrine infusions. Seven saline-tr eated (normal group) and 11 doxorubicin-treated rabbits (1 mg/kg admin istered intravenously twice weekly) were studied after 4 and 6 weeks' treatment. Five CHF rabbits received saline (C group) and 6 enalaprila t infusion (ACEI group) during each study period. After 4 weeks of dox orubicin, baroreflex-HR responses were normal, whereas baroreflex-NA s pillover responses were enhanced. Enalaprilat infusion shifted the HR- MAP curve downwards to the left but had no effect on the NA spillover- MAP curves. After 6 weeks of doxorubicin, when CHF was established, ba roreflex-HR and NA spillover curves were depressed. At this stage, ena laprilat had little effect on the HR-MAP curve bur restored towards no rmal the NA spillover-MAP curves. The results suggest that the endogen ous renin-angiotensin system contributes to attenuated baroreflex resp onses when CHF is established. (C) 1997 Elsevier Science B.V.