Cardiovascular Actions of Xamoterol (ICI 118,587) in Anaesthetized Cats, Rats, and Guinea Pigs

The maximal increases in heart rate produced by intravenous xamoterol in anaesthetized cats and rats are less than that of (-)-isoprenaline. In cats, blood pressure was slightly raised, while in rats, supramaximal cardiac-stimulant doses produced reductions in blood pressure. In anaesthetized guinea pigs, cardiac-stimulant effects of xamoterol were evident only after treatment with hexamethonium. In all three species cardiovascular responses to xamoterol were antagonized by beta-adrenoceptor antagonists. Thus, xamoterol is a partial agonist which displays beta 1-adrenoceptor selectivity. In cats, infusions of xamoterol elicited beta-adrenoceptor-mediated increases in heart rate, blood pressure, and cardiac output, while calculated total peripheral resistance was little affected and, unexpectedly, stroke volume was reduced. These cardiovascular effects were unaffected by hexamethonium or captopril. Both xamoterol and (-)-isoprenaline elevated left ventricular dP/dtmax and reduced central venous pressure. When cat heart rate was paced over a range (175-250 beats/min) corresponding to the beta-receptor-mediated chronotropic effects, an inverse relationship between rate and stroke volume was observed. The rate-induced reduction in stroke volume offers the best explanation for the decrease in stroke volume produced by xamoterol. In general, the effects of beta-adrenoceptor agonists on stroke volume in the anaesthetized cat appear to represent a balance between a rate-related reduction and a drug-induced elevation of this parameter.