Mechanisms of ventilatory inhibition by exogenous dopamine in cats

Intravenous injection of dopamine (DA) has consistently been shown to depress minute ventilation (VE). Whereas at low dosage (</=10 microgram/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 microgram/kg). The purpose of this study was to elucidate the mechanisms of DA-induced VE depression. The effects of intravenous injection of DA doses ranging from 1 to 200 microgram/kg were studied in 18 anesthetized cats. DA was injected during air and O2 breathing, after alpha-adrenergic blockade by phenoxybenzamine and after baro- and chemodenervation. VE and CSNCD were also simultaneously recorded on four occasions. In contrast to that with use of low-dose DA, VE 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, VE 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 VE depression induced by large-dose DA, in addition to its effects on arterial chemoreceptors. The contribution of baroreceptor stimulation and peripheral vasoconstriction is discussed.