Reduced hypotensive action of arachidonic acid in the spontaneously hypertensive rat.

SUMMARY Prostaglandins (PG) E, and I, are potent vasodepressor agents and their endogenous release may contribute to the regulation of blood pressure (BP). We Investigated whether a decreased response to or a decreased capacity of tbe rasculature to synthesize rasodepressor PGs could contribute to the increased vascular resistance characteristic of hypertension. The change in mean arterial blood pressure (MAP) to Intraaortic (i.a.) injection of PGE, and PGI, at 0.01, 0.1,1.0, and 10.0 and of sodium nitropnisside (NaNP) at0.1, 1.0 and 10.0 nmoles/100 g body weight (gbw) was measured in anesthetized, 30-week-old male rats of the spontaneously hypertensive (SHR), normotensive Wistar-Kyoto (WKY) and Wistar (W) strains. The percent decrease in MAP to equivalent doses of NaNP did not differ among the three strains of rats except at 1.0 nmole/100 gbw, a dose to which W rats showed a greater depressor response than either SHR or WKY rats. Similarly, no major differences were found among the strains in their response to the administration of PGI, except to a dose of 0.1 nmole/100 gbw to which both SHR and W rats responded with a greater percent decrease in MAP than WKY rats. In contrast, the percent decrease in MAP to PGE, was generally greater in SHR than WKY rats but was found not to differ between SHR and W rats at any dose. The i.a. injection of arachidonic acid (AA), while causing dose-dependent percent decreases in MAP in all strains, produced significantly smaller hypotensive responses at doses of 10 and 100 nmoles/100 gbw in SHR as compared to WKY or W rats. At doses of 300 nmoles AA or greater, hypotensive responses did not differ significantly between SHR or WKY rats whereas the W rat exhibited percent reductions in MAP that were significantly larger than those obtained in the other two strains of rats. We conclude that SHRs do not have a reduced ability to respond to exogenous PGE PGI or NaNP; however, SHRs appear to have a decreased capacity to utilize AA for the synthesis of vasodepressor PGs.