Mechanisms of ventilatory inhibition by exogenous dopamine in cats

Abstract

Intravenous injection of dopamine (DA) has consistently been shown to depress minute ventilation (V˙e). Whereas at low dosage (≤10 μg/kg) this effect may be accounted for by inhibition of the carotid sinus nerve chemosensory discharge (CSNCD), other mechanisms appear to be involved with large dosage (≥50 μg/kg). The purpose of this study was to elucidate the mechanisms of DA-inducedV˙e depression. The effects of intravenous injection of DA doses ranging from 1 to 200 μg/kg were studied in 18 anesthetized cats. DA was injected during air and O2 breathing, after α-adrenergic blockade by phenoxybenzamine and after baro- and chemodenervation.V˙e and CSNCD were also simultaneously recorded on four occasions. In contrast to that with use of low-dose DA, V˙e depression induced by high-dose DA was dissociated from CSNCD, persisted during 100% O2 breathing, and was significantly correlated with the rise in arterial blood pressure. Although blunted, V˙e depression was still present after complete chemo- and barodenervation but was suppressed by blocking of the concomitant vasoconstriction with phenoxybenzamine. It is concluded that reflexes of circulatory origin contribute to the V˙e depression induced by large-dose DA, in addition to its effects on arterial chemoreceptors. The contribution of baroreceptor stimulation and peripheral vasoconstriction is discussed.