Vascular Prostacyclin and Goldblatt Hypertensive Rats

Vascular prostacyclin production in Goldblatt hypertension was examined in one-kidney, one clip (1K,1C) and two-kidney, one clip (2K,1C) rat models. Vasodepressor responses to prostacyclin and nitroprusside correlated well with resting blood pressure in both groups of rats, but when measured as a percentage of resting blood pressure the responses did not differ significantly between hypertensive rats and the normotensive controls within each group. In contrast, the vasodepressor effects of arachidonic acid (1-3 mg/kg, i.v.) were much greater in the 1K,1C rats than in their normotensive controls, but did not differ significantly between hypertensive 2K,1C rats and sham-operated controls. The effects of arachidonic acid were virtually abolished by indomethacin (10 mg/kg, i.v.). The metabolism of [C]-arachidonic acid was also studied in isolated aortae of both one- and two-kidney rats by high pressure liquid chromatography of extracts of the incubation mixture. [C]-6-oxo-PGF1α was the only prostanoid conversion product recovered from the incubations and significantly more of this metabolite was produced by aortic tissue from 1K,1C rats than from normotensive controls. There was no difference in [C]-6-oxo-PGF2 α production between 2K,1C rats and controls. These results demonstrate an enhanced ability of vascular tissue from 1K,1C hypertensive rats to convert exogenous arachidonate to vasodilator prostacyclin, but this is not evident in the two-kidney model. Although enhanced biosynthetic capacity for prostacyclin in the one-kidney model and spontaneously hypertensive rats does not lessen peripheral vascular resistance, it might reflect a fundamental disturbance in phospholipid metabolism which contributes to increased vascular resistance.