RENAL MEDULLARY CAPTOPRIL DELIVERY LOWERS BLOOD-PRESSURE IN SPONTANEOUSLY HYPERTENSIVE RATS

We examined the contribution of renal medullary function to the mainte nance of hypertension in spontaneously hypertensive rats by infusing c aptopril chronically into the renal medullary interstitial space of un inephrectomized rats. Changes in cortical and medullary blood flow wer e determined using a newly developed optical fiber implantation techni que for laser-Doppler flowmetry. Renal medullary interstitial infusion of captopril (5 mg/kg per day) selectively increased medullary blood flow by 40% without altering renal cortical blood flow throughout the 5 days of captopril delivery. In association with the selective increa se of medullary perfusion, a significant natriuresis was observed on t he second day of the drug infusion, and urine osmolality was significa ntly reduced during the first 3 days of captopril infusion. Mean arter ial pressure was significantly decreased by 20 mm Hg during 5 days of captopril infusion, and the chronic renal function curve was shifted t o a lower level of arterial pressure compared with the control values when 0.9% sodium chloride saline vehicle was infused. Intravenously in fused captropril at 5 mg/kg per day did not alter mean arterial pressu re, excluding the possibility that the hypotensive effect of medullary captopril infusion was due to recirculation. In summary, chronic redu ction of the elevated renal medullary vascular tone by medullary inter stitial infusion of captopril reset the steady-state renal function cu rve and lowered arterial pressure in spontaneously hypertensive rats.