The primary objective of this investigation is to carry out in vitro studies of hypertension-induced changes in vascular smooth muscle and to verify the findings in vivo situation. The hypothesis to be tested is that changes in the responsiveness of the vascular smooth muscle is the primary causative factor in the development and maintainance of essential hypertension and that proper therapeutic management of the disease ought to be directed to the reversal of the alterations in the smooth muscle. The secondary long-term objective of this proposal is to develop our research laboratory into a major research center specializing in cardiovascular investigations in general and vascular smooth research in particular. Since hypertension is one of the major causes of death in the U.S.A., the health relatedness of the proposal is in synchrony with the goals of the National Institutes of Health in general and the National Institute of Blood and Lung in particular. Tangential primary objectives of the investigation is to train minority students in biomedical research and to establish a biomedical research base at Xavier University. The secondary objective is to develop and/or refine a cardiovascular method for measuring directly cardiovascular parameters in conscious rats and to apply the method in verifying some of our findings from in vitro studies in vivo conditions. The last objective is to investigate how the sympathetic activity is synchronized with the onset, maintenance and therapeutic reversal of hypertension. The methodology for studying the vascular smooth muscle will involve studies of in vitro preparations from genetically spontaneously hypertensive rats (SHR), age-matched normotensive controls and experimentally hypertensive rats using classical isolated organ bath techniques. We propose to use a new technique which we have developed to identify hypertension-induced changes and, to modify a cardiovascular technique for in vivo studies in rats. The developed cardiovascular technique will enable us to record directly cardiovascular parameters in conscious rat eliminating the interference from anesthetics. The data from hypertensive rats will be compared with those from normotensive control using student's t-test. Similarly, the data from treated animal will be compared with those from non-treated control using paired student's t-test.
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