KIDNEY IS AN IMPORTANT TARGET FOR THE ANTIHYPERTENSIVE ACTION OF AN ANGIOTENSIN-II RECEPTOR ANTAGONIST IN SPONTANEOUSLY HYPERTENSIVE RATS

Inhibitors of the renin-angiotensin system lower blood pressure of spo ntaneously hypertensive rats, although plasma renin is not elevated. T o test the hypothesis that the actions of angiotensin II within the ki dney may contribute to the high blood pressure in spontaneously hypert ensive rats, we infused valsartan, a subtype 1 angiotensin II receptor antagonist, via the suprarenal artery into the right kidney of consci ous, freely moving, unilaterally nephrectomized (left) spontaneously h ypertensive rats (12 to 14 weeks old). Valsartan (0.3 mg/kg per day fo r 48 hours) lowered blood pressure (change in blood pressure, -7+/-3, -19+/-4, and -26+/-4 mm Hg, n=11, at 12, 24, and 48 hours) after intra renal administration but had no significant effect on blood pressure a fter intravenous administration (change in blood pressure, 1+/-5, -3+/ -4, and 10+/-5 mm Hg, n=7, at 12, 24, and 48 hours). Infusion of vehic le (0.9% saline) intrarenally had no significant effect on blood press ure (change in blood pressure, 2+/-5, -1+/-6, and 0+/-7 mm Hg, n=11, a t 12, 24, and 48 hours). The maximum fall in blood pressure reached af ter intrarenal administration of this dose of valsartan was similar to the maximum fall induced after intravenous administration of higher d oses (change in blood pressure, -14+/-5, -27+/-4, and -32+/-5 mm Hg, n =7, at 12, 24, and 48 hours after 3 mg/kg per day i.v.). Thus, endogen ous angiotensin II acting within the kidney appears to play an importa nt role in the maintenance of high blood pressure in spontaneously hyp ertensive rats.