Effect of aging on endothelin-induced prostaglandin I2 release in isolated hind legs of the spontaneously hypertensive rat.

We evaluated the effect of aging on spontaneous release of prostaglandin I2 (PGI2; measured as 6-keto-PGF1a) as well as on endothelin-induced release of PGI2 from isolated hind legs perfused with Krebs-Ringer solution in 5-week-old, 10-week-old and 40-week-old Wistar-Kyoto rats (WKY) and age-matched spontaneously hypertensive rats (SHR). The spontaneous release of PGI2 was stable up to 40 minutes for both strains. The amount of the spontaneous release of PGI2 tended to fall with advancing age in WKY, while it remained unchanged in SHR. Porcine endothelin-1 (pET-1) added to the perfusion medium (2 x 10(-12)-2 x 10(-10) M) increased PGI2 release in a dose-dependent fashion in both strains regardless of age. However, the maximal increase of PGI2 release evoked by endothelin (2 x 10(-10) M) was significantly greater in 40-week-old SHR compared with age-matched WKY. These results not only suggest that there exists a much greater reservoir of vascular PGI2 synthesis in SHR, but also imply that the enhanced release of PGI2 in response to endothelin, the most potent vasoconstrictor known, may function as a factor or a modulator to attenuate endothelin-induced vasoconstriction in senescent SHR.