Depression of efferent parasympathetic control of heart rate in rats with myocardial infarction: effect of losartan

Journal of Cardiovascular Pharmacology
X J DuM D Esler

Abstract

Heart failure is associated with attenuation of parasympathetic nervous function and enhanced renin-angiotensin activity. We tested whether there was a dysfunction in the efferent cholinergic neurotransmission in the heart of rats with chronic myocardial infarction (MI) and the potential role of angiotensin II (Ang II) receptors in such changes. Rats with MI and sham-operation were anesthetized, and heart rate (HR) reduction in response to vagal nerve stimulation was measured before and after losartan administration (10 mg/kg, i.v.) in the presence or absence of physostigmine to inhibit acetylcholinesterase. Infarcted rats had an average infarct size (IS) of 38% of the left ventricle (LV), depressed LV dP/dtmax, elevated LVEDP, and cardiac hypertrophy. Nerve stimulation (1-16 Hz) reduced HR in a frequency-dependent manner. The bradycardiac responses were significantly attenuated in infarcted versus control rats (p < 0.01), indicating an impaired efferent vagal tone. In contrast, the bradycardic response to exogenous acetylcholine was similar in both groups, implying an unchanged muscarinic receptor responsiveness in hearts with MI. HR response to nerve stimulation was potentiated by losartan in infarcted rats by 21 +/- 4 versus...Continue Reading

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Citations

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