We propose to test the hypothesis that the hypertension occurring with age results from dysfunction of brain aminergic mechanisms which normally regulate sympathetic vasomotor tone and blood pressure. Whether blood pressure also rises with age in rats, as it does in man, will first be determined by using a properly validated tail-cuff method to monitor blood pressure in different groups of aging Sprague-Dawley and Fischer 344 rats. To test for central dysfunction, cardiovascular and sympathetic nerve responses elicited by stimulating various hypothalamic and medullary centers electrically will be compared with those from younger rats of the same strain. Baroreflex sensitivity will be assessed by recording chronotropic and sympathetic nerve responses produced reflexly as blood pressure is elevated with phenylephrine or lowered with sodium nitroprusside; these baroreflex responses would then be compared with those obtained from younger normotensive or hypertensive rats. Acute and long-term effects of sinoaortic denervation (SAD) on regional hemodynamics, plasma catecholamines, and renin concentration will be measured. Brain amine synthesis and metabolism will be evaluated following renal denervation or arterial stenosis to determine whether aberrant signals from the kidneys contribute to alter central cardiovascular regulation in aged rats. If a good model for simulating the blood pressure elevation that occurs with age can be developed in rats, the model can be used to obtain information that could improve our understanding of age-related cardiovascular dysfunction and help us find ways to reduce mortality and morbidity caused by hypertension in the elderly.
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