Altered vascular reactivity has frequently been suggested to contribute to the elevated peripheral vascular resistance that is characteristic of hypertension (1-7). Structural changes in arteries due to increased wall stress may be responsible in part for altered responsiveness of the vasculature in hypertension; however, functional changes in the sensitivity of vascular smooth muscle, particularly in resistance vessels, may also contribute significantly to the etiology of the disease. Increased sensitivity to norepinephrine (24,27) and to calcium ion (Ca; 25,28), and decrease relaxation in response to acetylcholine and hydralazine (29) have been reported in isolated mesenteric resistance vessels from SHR. The present proposal seeks to determine whether these changes in SHR resistance vessels are related to altered Ca handling through the study of 45Ca fluxes. Other possible changes in responses to vasoconstrictor and vasodilator agents in these vessels from SHR (6 and 16 week old) will also be investigated further through the study of 45Ca fluxes. Most of the previous work characterizing changes in the handling of Ca associated with contrictile changes in isolated vessels in hypertension has described aorta or other conduit arteries. It should be of great value to so characterize isolated resistance vessels, since they are primarily responsible for the elevated peripheral vascular resistance in hypertension. Moreover, we now know that resistance vessels utilize Ca for contraction very differently from conduit vessels (57), which further necessitates the study of contractile responses and 45Ca fluzes in resistance vessels. Moreover, the effects of organic Ca antagonists on tension and 45Ca fluxes in resistance vessels will be very valuable, since these agents have received increasing attention recently as possible therapeutic agents in the treatment of human hypertension (30).
