title: 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.
authors.affiliation: Monash University Department of Medicine, Monash Medical Centre, Clayton, Vic., Australia.
authors.forename: T
authors.initials: T
authors.lastname: Noshiro
authors.forename: D
authors.initials: D
authors.lastname: Way
authors.forename: B P
authors.initials: BP
authors.lastname: McGrath
mesh_terms: D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000633:toxicity; D017704:Baroreflex / Q000187:drug effects / Q000502:physiology*; D001794:Blood Pressure / Q000187:drug effects; D004317:Doxorubicin / Q000633:toxicity; D015773:Enalaprilat / Q000494:pharmacology; D006333:Heart Failure / Q000139:chemically induced / Q000378:metabolism* / Q000503:physiopathology*; D006339:Heart Rate / Q000187:drug effects; D009599:Nitroprusside / Q000494:pharmacology; D009638:Norepinephrine / Q000378:metabolism*; D010656:Phenylephrine / Q000494:pharmacology; D011817:Rabbits; D012039:Regional Blood Flow / Q000187:drug effects; D012079:Renal Circulation / Q000187:drug effects / Q000502:physiology; D012084:Renin-Angiotensin System / Q000187:drug effects / Q000502:physiology
chemical_list: D000316:Adrenergic alpha-Agonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D000903:Antibiotics, Antineoplastic; D009599:Nitroprusside; D010656:Phenylephrine; D004317:Doxorubicin; D015773:Enalaprilat; D009638:Norepinephrine