R. Munozgarcia et al., ACUTE RENAL EXCRETORY ACTIONS OF IOSARTAN IN SPONTANEOUSLY HYPERTENSIVE RATS - ROLE OF AT(2) RECEPTORS, PROSTAGLANDINS, KININS AND NITRIC-OXIDE, Journal of hypertension, 13(12), 1995, pp. 1779-1784
Aim: The effects of losartan on blood pressure and on renal function h
ave mainly been attributed to AT(1) receptor blockade. Experimental ev
idence suggests that these effects could also be related to the action
s of angiotensin II through AT(2) receptors or to vasodilatory systems
. The present study was therefore designed to investigate the manner i
n which the acute effects of losartan on renal excretory function are
affected during simultaneous administration of an AT(2) receptor antag
onist, a kinin B-2 receptor antagonist, a cyclo-oxygenase inhibitor or
a nitric oxide synthesis inhibitor. Materials and methods: The AT(2)
receptor antagonist PD 123319 (10mg/kg), the bradykinin B-2 receptor a
ntagonist Hoe 140 (30 mu g/kg), the cyclo-oxygenase inhibitor meclofen
amate (5 mg/kg) and the nitric oxide synthesis inhibitor N-G-monomethy
l-L-arginine (1 mu g/kg per min) were administered separately with acu
te intravenous losartan (1 mg/kg) to spontaneously hypertensive rats a
nd the effects on mean arterial pressure and renal excretory function
were assessed. Results: Losartan reduced mean arterial pressure by 11.
1 +/- 5.7 mmHg and increased the glomerular filtration rate, urine flo
w and sodium excretion rate. The decrease in mean arterial pressure wa
s blocked in the presence of N-G-monomethyl-L-arginine but not during
concurrent administration of PD 123319, Hoe 140 or meclofenamate. The
increase in glomerular filtration rate induced by losartan was blunted
by Hoe 140, meclofenamate and Nc-monomethyl-L-arginine. Go-administra
tion of PD 123319, Hoe 140 or meclofenamate, but not of Nc-monomethyl-
L-arginine, partially blunted the diuresis and natriuresis induced by
losartan.Conclusions: Nitric oxide participates in the antihypertensiv
e action of losartan. Kinins, prostaglandins and nitric oxide appear t
o be involved in the effects of losartan on the glomerular filtration
rate. The increases in urine flow and sodium excretion rate induced by
losartan depend partially on AT(2) receptors, kinins and prostaglandi
ns.