Angiotensin II-induced hypertension in the rat. Effects on the plasma concentration, renal excretion, and tissue release of prostaglandins

Abstract

We examined in rats the effects of intraperitoneal angiotensin II (AII) infusion for 12 d on urinary excretion, plasma concentration, and in vitro release of prostaglandin (PG) E2 and 6-keto-PGF(1α), a PGI2 metabolite. AII at 200 ng/min increased systolic blood pressure (SBP) progressively from 125 ± 3 to 170 ± 9 mmHg (P < 0.01) and elevated fluid intake and urine volume. Urinary 6-keto-PGF(1α) excretion increased from 38 ± 6 to 55 ± 5 and 51 ± 7 ng/d (P < 0.05) on days 8 and 11, respectively, of AII infusion, but urinary PGE2 excretion did not change. Relative to a control value of 129 ± 12 pg/ml in vehicle-infused (V) rats, arterial plasma 6-keto-PGF(1α) concentration increased by 133% (P < 0.01) with AII infusion. Aortic rings from AII-infused rats released more 6-keto-PGF(1α) (68 ± 7 ng/mg) during 15-min incubation in Krebs solution than did rings from V rats (40 ± 3 ng/mg); release of PGE2, which was < 1% of that of 6-keto-PGF(1α), was also increased. Slices of inner renal medulla from AII-infused rats released more 6-keto-PGF(1α) (14 ± 1 ng/mg) during incubation than did slices from V rats (8 ± 1 ng/mg, P < 0.05), but PGE2 release was not altered. In contrast, AII infusion did not alter release of 6-keto-PGF(1α) or PGE2 from inferior vena cava segments or from renal cortex slices. Infusion of AII at 125 ng/min also increased SBP, plasma 6-keto PGE(1α) concentration, and in vitro release of 6-keto PGF(1α) from rings of aorta and renal inner medulla slices; at 75 ng/min AII had no effect. SBP on AII infusion day 11 correlated positively with both 6-keto-PGF(1α) plasma concentration (r = 0.54) and net aortic ring release (r = 0.70) when data from all rats were combined. We conclude that augmentation of PGI2 production is a feature of AII-induced hypertension. The enhancement of PGI2 production may be an expression of nonspecific alteration in vascular structure and metabolic functions during AII-induced hypertension, as well as the result of a specific effect of the peptide on the arachidonate-prostaglandin system.