The effects of anaesthetics on the reactivity of vascular smooth muscle

This thesis examines a number of aspects of vascular smooth muscle physiology and pharmacology. The first set of experiments examines the mechanisims of the myogenic response in the isolated pressurised rabbit ear artery preparation, an experimental model developed here in the University of Tasmania, Department of Physiology. Rabbit ear artery segments were subjected to pressure changes in the form of either rapid increases (referred to as jumps) or slow increases (ramps). The changes in diameter of vessels as they responded to these pressure alterations were recorded. These same pressure changes were performed in vessels in four settings: in vessels where the endothelium had been removed, in vessels constricted with different vasoconstrictor agents, and at different starting diameters, in vessels dilated with either acetylcholine or sodium nitroprusside, and in vessels partly dilated with the calcium channel blocking agent, nifedipine. The results demonstrated that the endothelium was not mandatory for the myogenic response, but that acetylcholine induced endotheliumderived relaxing factor release could modify the nature of the response, as could nifedipine. The nature of vasoconstriction, and degree of constriction of the vessels were not major determinants of myogenicity. The effect of the intravenous anaesthetic agent propofol on vascular smooth muscle was then examined. This relatively recently introduced drug is known to possess significant hypotensive properties, but the mechanism of this response is unclear. In a series of experiments using the rabbit ear artery preparation, it was found that apart from having a direct vasodilator effect, propofol was a powerful attenuator of myogenicity - an effect distinct from its smooth muscle relaxant properties. This may be important in explaining the drugs hypotensive effect. Lastly, a series of experiments used the experimental apparatus to examine the effects of intra-arterial drug administration of both propofol and thiopentone. Intra-arterial administration of propofol, from clinical reports does not appear to be associated with serious hazard, a finding, in part confirmed by studies performed in this series. However, intra-arterial thiopentone administration was found to result in an almost complete destruction of the vascular endotheliuman hitherto unreported event which may well explain the reasons for the widespread vascular damage and ischaemia associated with accidental intra-arterial injection.