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 spontaneously hypertensive rats, although plasma renin is not elevated. To test the hypothesis that the actions of angiotensin II within the kidney may contribute to the high blood pressure in spontaneously hypertensive rats, we infused valsartan, a subtype 1 angiotensin II receptor antagonist, via the suprarenal artery into the right kidney of conscious, freely moving, unilaterally nephrectomized (left) spontaneously hypertensive rats (12 to 14 weeks old). Valsartan (0.3 mg/kg per day for 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 intrarenal administration but had no significant effect on blood pressure after 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 vehicle (0.9% saline) intrarenally had no significant effect on blood pressure (change in blood pressure, 2 +/- 5, -1 +/- 6, and 0 +/- 7 mm Hg, n = 11, at 12, 24, and 48 hours). The maximum fall in blood pressure reached after intrarenal administration of this dose of valsartan was similar to the maximum fall induced after intravenous administration of higher doses (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, endogenous angiotensin II acting within the kidney appears to play an important role in the maintenance of high blood pressure in spontaneously hypertensive rats.
Department of Cardiovascular Research, CIBA GEIGY Ltd., Basel, Switzerland.
J M
JM
Wood
C R
CR
Schnell
N R
NR
Levens
D000804:Angiotensin II / Q000494:pharmacology; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D007262:Infusions, Intravenous; D007267:Injections; D007668:Kidney / Q000187:drug effects*; D008297:Male; D051381:Rats; D011918:Rats, Inbred SHR / Q000502:physiology*; D012083:Renin / Q000097:blood; D013777:Tetrazoles / Q000097:blood / Q000494:pharmacology; D014633:Valine / Q000031:analogs & derivatives / Q000097:blood / Q000494:pharmacology; D000068756:Valsartan
D057911:Angiotensin Receptor Antagonists; D000959:Antihypertensive Agents; D013777:Tetrazoles; D000804:Angiotensin II; D000068756:Valsartan; D012083:Renin; D014633:Valine