Angiotensin II/prostaglandin I2 interactions in spontaneously hypertensive rats.

The purpose of this study was to compare the effects of prostaglandin I2 on several cardiovascular parameters and to compare the ability of prostaglandin I2 to modify angiotensin II-induced changes in these cardiovascular parameters in spontaneously hypertensive versus normotensive rats. Studies were conducted in adult, age-matched, indomethacin-, and captopril-pretreated spontaneously hypertensive and normotensive rats that had been prepared for assessment of arterial blood pressure, cardiac output (thermodilution), and renal and mesenteric blood flows (transit-time flow probes). In both normotensive and hypertensive rats, intravenous infusions of prostaglandin I2 (0.003, 0.03, 0.3, 1, 3, and 10 micrograms/kg per minute) dose-dependently reduced mean arterial blood pressure, total peripheral resistance, and mesenteric vascular resistance but not renal vascular resistance. Only minor differences were detected between normotensive versus hypertensive rats with regard to the effects of prostaglandin I2 on baseline cardiovascular parameters (ie, in the absence of angiotensin II). In both rat strains, an intravenous infusion of angiotensin II (300 ng/kg per minute) increased mean arterial blood pressure, total peripheral resistance, and renal and mesenteric vascular resistances, and these effects of angiotensin II were similar in the two strains in the absence of prostaglandin I2. In both strains, prostaglandin I2 inhibited angiotensin II-induced changes in mean arterial blood pressure, total peripheral resistance, and renal and mesenteric vascular resistances. However, in the renal, but not mesenteric, vasculature of hypertensive rats, the ability of prostaglandin I2 to attenuate angiotensin II-induced vasoconstriction was strikingly reduced. These results indicate that although in general spontaneously hypertensive rats respond normally to prostaglandin I2, in the kidney of spontaneously hypertensive rats the ability of prostaglandin I2 to attenuate angiotensin II-induced vasoconstriction is reduced. This selective renal defect may relate to the pathogenesis of high blood pressure in this genetic model of hypertension.