Alterations in the response of arterioles and resistance arteries to changes in PO2 may contribute to the development and maintenance of an elevated vascular resistance and adversely affect the ability of peripheral vascular beds to regulate tissue perfusion in hypertension. This project seeks to elucidate the mechanisms regulating active tone in resistance arteries and in situ arterioles during changes in PO2, and to determine how these mechanisms are altered in hypertension. The role of vascular smooth muscle (VSM) transmembrane potential (E/m) in mediating vessel responses to altered PO2, will be assessed by measuring diameter and VSM E/m in isolated cerebral and skeletal muscle resistance arteries of hypertensive and normotensive rats during simultaneous increases or stepwise reductions in the PO2, of the physiological salt solution perfusing and superfusing the vessel. The response of in situ cremasteric arterioles to altered PO2, will be determined by measuring diameter and VSM E/m during elevations of superfusate PO2 or changes in systemic arterial PO2 produced by increasing or reducing the fraction of O2 in the inspired air at a constant arterial PCO2. The role of pressure in modulating vascular responses to altered PO2 will be tested by measuring diameter and VSM E/m in isolated resistance arteries as PO2 is changed at different levels of intravascular pressure. The role of shear stress in modulating vascular responses to changes in PO2 will be assessed by determining the response of isolated resistance arteries and in situ arterioles to increased flow during conditions of altered O2 availability. The role of the endothelium in mediating hypoxic relaxation of resistance arteries will be assessed by determining vessel responses to reduced PO2 before and after endothelial removal, and by measuring arachidonic acid metabolites produced by the vessels during exposure to reduced PO2. The sensitivity of resistance arteries of hypertensive and normotensive animals to vasodilator prostaglandins will also be tested to determine whether the reduced dilation of arteries of the hypertensive animals in response to decreased PO2 is due to a reduced sensitivity of the vessels to vasodilator eicosanoids.
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