(Circulation. 1995;91:2655-2663.)
© 1995 American Heart Association, Inc.
Articles |
Selective Impairment of Vagally Mediated, Nitric Oxide–Dependent Coronary Vasodilation in Conscious Dogs After Pacing-Induced Heart Failure
From the Department of Physiology, New York Medical College, Valhalla, NY.
Correspondence to Thomas H. Hintze, PhD, Department of Physiology, New York Medical College, Valhalla, NY 10595.
Background Activation in conscious dogs of the carotid chemoreflex or cardiac receptors results in coronary vasodilation that is mediated by a vagal cholinergic mechanism. Our previous study showed that the coronary vasodilation following activation of carotid chemoreflex is also mediated by nitric oxide (NO). In addition, NO production is depressed after the development of heart failure. Therefore, we hypothesized that the coronary vasodilation after activation of reflexes that elicit efferent vagal coronary vasodilation would be blunted in conscious dogs after pacing-induced heart failure due to the disappearance of NO.
Methods and Results Mongrel dogs were chronically instrumented using sterile techniques for measurements of systemic hemodynamics and left circumflex coronary blood flow (CBF). Without the heart rate controlled, intra-atrial injection of veratrine (4 µg/kg) caused bradycardia (-36±3 beats per minute). With the heart rate controlled, veratrine increased CBF in a dose-dependent manner: for example, 4 µg/kg of veratrine increased CBF by 54±5% from 38±4.9 mL/min (P<.05). The increases in CBF induced by veratrine were markedly blunted by nitro-L-arginine (NLA). Activation of carotid chemoreflex by nicotine increased CBF by 121±9% from 32±4 mL/min (P<.05) with the heart rate controlled and caused bradycardia (-32±5 beats per minute) without the heart rate controlled. After the development of heart failure, in response to activation of carotid chemoreflex or cardiac receptors the coronary vasodilation was almost abolished (CBF increased by only 23±8% or 11±3%, P<.05 compared with control). There still was a marked bradycardia after injections of nicotine or veratrine (-50±11 or -48±7 beats per minute).
Conclusions Our results indicate that vagally mediated coronary vasodilation is selectively attenuated in conscious dogs after pacing-induced heart failure, whereas the vagally mediated bradycardia is preserved. Since muscarinic receptor–induced coronary vasodilation is mediated by NO, the disappearance of NO from blood vessels leads to a defect in the integrated neural regulation of coronary blood flow and myocardial function during heart failure.
Key Words: nicotine • carotid arteries • reflex • endothelium-derived factors • veratrine
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