Effects of the Antihypertensive Prostaglandin Analog Ro 22-1327 on Regional Blood Flows in the Spontaneously Hypertensive Rat

Abstract

The hemodynamic effects of Ro 22-1327 [nat-(15R,16R)-16-fluoro-15-hydroxy-9-oxoprosta-5(Z),13(E)-dienoic acid], a prostaglandin E2 analog, were evaluated in anesthetized spontaneously hypertensive rats (SHR). Within 3-4 h of topical application (1 and 3 mg/kg), a dose-dependent decrease in mean arterial blood pressure was observed. At 6 h following drug application, steady-state mean arterial pressure was 79-87% of control (pretreatment) values. Increments in blood flow, as well as reductions in vascular resistance, were apparent in the kidneys, skin, and the majority of the splanchnic organs. The magnitude of the drug-induced hyperemia decreased from the duodenum to the ileum. Significant elevations in colonic blood flow were not apparent with either dose, suggesting a proximal-to-distal gradient of response of the intestinal vasculature to the drug. The results of this study indicate that Ro 22-1327 is an effective antihypertensive agent when applied topically in SHR. Our results also imply that the splanchnic vascular bed contributes heavily to the antihypertensive activity of the compound.