AuthorHYNES, MICHAEL RAY.
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PublisherThe University of Arizona.
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AbstractDilation of blood vessels in response to a large number of agents has been shown to be dependent on an intact vascular endothelium. The present studies examine some aspects of endothelium-dependent vasodilation in blood vessels of the rabbit and rat. Using the rabbit ear artery and the subtype-selective muscarinic antagonist pirenzepine, muscarinic receptors of the endothelium and smooth muscle cells were shown to be of the low affinity M₂ subtype. Inhibition of [³H](-)quinuclidinyl benzilate was used to determine affinity for the smooth muscle receptors while antagonism of methacholine induced vasodilation yielded the endothelial cell receptor affinity. The effect of increasing age (1-27 months) on endothelium-dependent relaxation was studied in aortic rings, perfused tail artery and perfused mesenteric bed of the Fisher 344 rat. Both aortic ring segments and perfused caudal arteries showed an age-related increase in sensitivity of endothelium-mediated relaxation to the cholinergic agonist methacholine. This increased sensitivity occurs between the ages of 6 and 12 months, with no further significant increase up to 27 months of age, suggesting this is a consequence of growth and development rather than old age. No difference with age in cholinergic relaxation was observed in the perfused mesenteric bed indicating either no change of sensitivity in smaller resistance vessels or an effect which is hidden in this more complex perfused system. In contrast to findings with cholinergic stimution, responses of the perfused caudal artery to the calcium ionophore A23187 were not altered with age. This suggests that the alteration with age in response to methacholine involves the muscarinic receptor or receptor coupling mechanism rather than the generation of, or response to, endothelium-derived relaxing factor (EDRF). The influence of endothelium on contractile responses was examined using the perfused caudal artery. Endothelium removal significantly increased contraction to the α-adrenergic agonists methoxamine and BH-T 920 as well as to transmural nerve stimulation. Inhibition of contraction to agents which must first cross the smooth muscle layer before reaching the endothelium suggests that a continuous or basal level of EDRF release is responsible for decreased contraction rather than an receptor stimulated release of EDRF.
Degree ProgramPharmacology and Toxicology