MINORITY SCHOOL FACULTY DEVELOPMENT AWARD

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The objectives of the proposed studies are threefold: a) to examine the long term effect of arachidonic acid (AA) and eicosapentaenoic acid (EPA) on blood pressure of hypertensive rats (SHR) and stroke prone spontaneously hypertensive rats (SHRSP), b) to examine the discrete hemodynamic consequences (organ blood flow and cardiac functions) of chronic supplementation of AA and EPA, c) to examine metabolic and neuroendocrine consequences of chronic AA and EPA administration. These objectives will be addressed by specific experiments in which SHR, SHRSP and normotensive rats will be given (s.c.) daily injections of AA or EPA. Blood pressure (BP) and heart rate (HR) will be followed for 3 months by tail-plethysmography and at the end of the experiments by direct measurements of the following hemodynamic measurements: BP, HR, cardiac output (CO) and discrete organ blood flow (renal, mesenteric, hindquarter). In addition, the activity of the sympathetic nervous systems will be assessed by direct measurements of plasma levels of catecholamines (norepinephrine, epinephrine and dompamine). These aims will be achieved as follows: Direct measurements of BP, HR and CO will be done in conscious rats. Blood flow to discrete organs (renal, mesenteric, hindquarters) will be done by the directional pulsed Doppler technique using VF-microprobes implanted on the respective arteries (microsurgery under anesthesia). Biochemical and endocrine status will be assessed by withdrawal of blood from arterial lines implanted in the femoral artery. Catecholamines will be assayed by the radioenzymatic-TLC method. Prostaglandins (PGE2, 6-keto-PGF1 and TXB2) will be assayed on plasma samples and in an ex-vivo system where tissue samples of AA and EPA treated and control rats are incubated in-vitro. These studies will provide new insights on the mechanism of the hypotensive effects of the major polyunsaturated fatty acid (PUFA)-AA and EPA, and its relationship to prostaglandins, and the sympatho-adrenomedullary system. It will provide absolutely new data on cardiac functions and organ blood flow response to PUFA in experimental models of stroke and hypertension and will eventually indicate the beneficial long term protective effect of PUFAs against stroke. Since AA and EPA are essential nutrients, this study might support a dietary approach to prevention or therapy of too major cardiovascular diseases: stroke and hypertension.