A Differential Effect of Chronically Administered Guanethidine on Sympathetic Neurotransmission to the Dog Heart and Mesenteric Arterial Blood Vessels

Abstract

The responsiveness of the dog heart and isolated perfused mesenteric arteries to adrenergic nerve stimulation was studied following chronic oral guanethidine administration (2.5 mg/kg per day). Treatment for 1 week abolished the mesenteric arterial vasoconstrictor response to periarterial nerve stimulation and attenuated markedly the chronotropic effect resulting from stimulation of the cardioaccelerator nerves. After 6 months, the positive chronotropic response to cardiac nerve stimulation was restored to within control values, whereas complete adrenergic neuronal blockade persisted in the mesenteric arteries. Resting heart rate and the cardiovascular responses to bilateral carotid occlusion (B.C.O.) were depressed at 1 week, but after 6 months, both the resting heart rate and the positive chronotropic response to B.C.O. were restored. However, the systemic blood pressure rise to B.C.O. remained inhibited. Biochemical and histochemical studies failed to reveal any recovery in cardiac norepinephrine (NE) content, and changes in the cardiovascular responsiveness to intravenous NE seemed largely independent of the duration of drug treatment. At 6 months, the heart rate and depressor responses to intravenous isoproterenol were unchanged, indicating the absence of any detectable postsynaptic supersensitivity.The results show a clear differential effect of chronically administered guanethidine on the sympathetic innervation to the heart compared with the mesenteric arterial blood vessels, thus underlining the importance of evaluating drug effects on a chronic basis.