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The aim of this study was to examine the effects of heparin on blood pressure in spontaneously hypertensive rats (SHR). Chronic subcutaneous administration of heparin consistenly lowers blood pressure in hypertensive rats. This antihypertensive effect is related at least in part to a concomitant decrease in hematocrit. Spontaneously hypertensive rats were treated with subcutaneous heparin (700U/day) for 6 weeks. At the end of this period we determined cardiac output and total peripheral resistance. Weekly determinations of systolic blood pressure (tail-cuff) and hematocrit were done. Peripheral plasma renin activity, plasma aldosterone, plasma prostaglandins, and urinary kallikrein were measured. Blood pressure responses of acute and chronic heparin treatment to vasoconstrictor substances, including angiotensin I, angiotensin II and norepinephrine, were determined. Heparin produced a significant decrease in hematocrit and a parallel decrease in blood pressure. A significant increase in plasma renin activity was found in heparin treated SHR, but plasma aldosterone level significantly decreased. Plasma prostaglandins and urinary kallikrein levels were not different among the groups. The blood pressure responses to vasoactive substances were similar among the heparin treated and control groups. The results suggest that a reduced aldosterone level contributes to the antihypertensive mechanism of heparin.