MECHANISMS OF VENTILATORY INHIBITION BY EXOGENOUS DOPAMINE IN CATS

Intravenous injection of dopamine (DA) has consistently been shown to depress minute ventilation ((V) over dot E). Whereas at low dosage (le ss than or equal to 10 mu g/kg) this effect may be accounted for by in hibition of the carotid sinus nerve chemosensory discharge (CSNCD), ot her mechanisms appear to be involved with large dosage (greater than o r equal to 50 mu g/kg). The purpose of this study was to elucidate the mechanisms of DA-indueed (V) over dot E depression. The effects of in travenous injection of DA doses ranging from 1 to 200 mu g/kg were stu died in 18 anesthetized cats. DA was injected during air and O-2 breat hing, after a-adrenergic blockade by phenoxybenzamine and after bare-a nd chemodenervation. (V) over dot E and CSNCD were also simultaneously recorded on four occasions. In contrast to that with use of low-dose DA, (V) over dot E depression induced by high-dose DA was dissociated from CSNCD, persisted during 100% O-2 breathing, and was significantly correlated with the rise in arterial blood pressure. Although blunted , (V) over dot E depression was still present after complete chemo-and barodenervation but was suppressed by blocking of the concomitant vas oconstriction with phenoxybenzamine. It is concluded that reflexes of circulatory origin contribute to the (V) over dot E depression induced by large-dose DA, in addition to its effects on arterial chemorecepto rs. The contribution of baroreceptor stimulation and peripheral vasoco nstriction is discussed.