Angiotensin converting enzyme inhibition improves baroreflex-induced noradrenaline spillover responses in rabbits with heart failure

Abstract

Impaired baroreflex function is a characteristic feature of congestive heart failure (CHF), although the mechanism is obscure. This study examined 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-mediated changes in heart rate (HR), total and renal noradrenaline (NA) spillover rates were examined in conscious rabbits with doxorubicin-induced cardiomyopathic CHF. Studies were performed under resting conditions and in response to changes in mean arterial pressure (MAP) induced by sodium nitroprusside and phenylephrine infusions. Seven saline-treated (normal group) and 11 doxorubicin-treated rabbits (1 mg/kg administered intravenously twice weekly) were studied after 4 and 6 weeks' treatment. Five CHF rabbits received saline (C group) and 6 enalaprilat infusion (ACEI group) during each study period. After 4 weeks of doxorubicin, baroreflex-HR responses were normal, whereas baroreflex-NA spillover 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, baroreflex-HR and NA spillover curves were depressed. At this stage, enalaprilat had little effect on the HR–MAP curve but restored towards normal the NA spillover–MAP curves. The results suggest that the endogenous renin–angiotensin system contributes to attenuated baroreflex responses when CHF is established.