Purinergic control of smooth muscle tone in different-sized rat mesenteric arteries

It is known that different-sized blood vessels performs different functions within the circulation. Analysis of the literature suggests that there are diameter-dependent differences in the characteristics of neuronal regulation of arterial smooth muscle tone. The experiments described in this thesis were designed to investigate this by systematically studying the neuronal control of arterial tone in three sizes of artery using the rat mesentery as a model vascular bed. The role of purinergic transmission was of particular interest. My experiments show that ,-meATP and suramin are far less potent in large arteries than in smaller vessels. Contractions evoked by brief trains of nerve stimulation are mainly purinergic in small and medium-sized arteries but almost entirely adrenergic in large arteries. Investigations of the sources of calcium for contraction revealed that blockade of L-type calcium channels has very little effect on agonist or nerve-evoked contractions. Inhibition of calcium-induced calcium release also caused hardly any reduction of contractile responses. Despite the pharmacological differences observed in whole tissue experiment, immunohistochemical analysis showed no substantial differences in the expression pattern of P2X receptor isoforms in the three sizes of artery. Electrophysiological experiments indicate that P2X current densities are broadly similar in all arteries, and in contrast to contraction studies, currents were always suramin sensitive. In addition, all post-junctional responses to P2X receptor agonist are abolished in vas deferens from P2X1-deficient mice. The two main conclusions that can be drawn from my data are i) purinergic transmission is more important in sympathetic nerve-mediated control of arterial tone in small arteries which are crucial in blood pressure regulation ii) almost all the calcium required for smooth muscle contraction is provided by calcium entry through the P2X receptor channel. This may have important implications for the treatment of hypertension.