Autonomic and haemodynamic responses to SK & F 101468 (ropinirole), a DA2 agonist, in anaesthetised cats.

The haemodynamic and autonomic nervous system effects of the DA2 agonist, SK & F 101468, have been studied in anaesthetised cats. SK & F 101468 inhibited the tachycardia response to cardiac accelerans nerve stimulation. The inhibition, reversed by L-sulpiride a selective DA2 receptor antagonist, was dose-dependent over the dose range 10-50 micrograms.kg-1 and there was proportionally greater inhibition of the responses to low rather than high frequency stimulation. There was evidence that SK & F 101468-A inhibited sympathetically mediated reflexes, but even at high doses, of up to 500 micrograms.kg-1, there was no inhibition of end-organ responsiveness to noradrenaline, isoprenaline or acetylcholine nor of the bradycardia caused by vagus nerve stimulation. SK & F 101468-A produced falls in blood pressure and heart rate at 50 and 500 micrograms.kg-1, but stroke volume, aortic blood flow and total peripheral resistance, were only slightly affected. These effects of SK & F 101468 in the intact cardiovascular system are consistent with an action on presynaptic receptors at sympathetic nerve endings to reduce transmitter release and thereby selectively reduce responses to sympathetic nerve stimulation.

In vivo pharmacological studies with SK&F 94836, a potent inotrope/vasodilator with a sustained duration of action.

1. SK&F 94836 (racemate) was studied in vivo for its cardiovascular properties in cats and dogs. 2. In anaesthetized cats and dogs SK&F 94836 administered intravenously caused increases in left ventricular contractility and decreases in peripheral vascular resistance at similar doses, thus demonstrating the compound to be a mixed acting positive inotropic/vasodilator agent. 3. In conscious instrumented dogs SK&F 94836 was active via the oral as well as intravenous route. 4. The inodilator activity of SK&F 94836 in conscious and anaesthetized animals occurred in association with minimal changes in either blood pressure or heart rate. 5. Detailed studies carried out on anaesthetized cats indicated that SK&F 94836 caused a balanced dilatation of both resistance and capacitance blood vessels. 6. Haemodynamic studies in anaesthetized cats indicated that as a consequence of the inotropic/vasodilator actions, SK&F 94836 caused significant increases in cardiac output and stroke volume. 7. Detailed studies in anaesthetized dogs indicated that significant inodilator activity occurred in the absence of an increase in myocardial oxygen consumption. 8. The duration of action of SK&F 94836 was sustained following both i.v. and oral administration. 9. We conclude that SK&F 94836, as an orally active inotropic/vasodilator agent with a sustained duration in vivo, has potential utility in the treatment of congestive heart failure.