Differences in arachidonic acid metabolism and effects of aspirin between one- and two-kidney Goldblatt hypertensive rats.

Vasodepressor responses to prostacyclin, nitroprusside and arachidonic acid were compared in two groups of anaesthetized, two-kidney, one-clip Goldblatt rats. The groups were composed of rats which had high blood pressure (greater than 150 mmHg systolic) or normal blood pressure (less than 140 mmHg systolic). The vasodepressor effects of prostacyclin and nitroprusside and arachidonic acid did not differ significantly between hypertensive and normotensive groups when measured as percentages of resting blood pressure. Thus, in contrast to one-kidney Goldblatt hypertensive rats, there is no evidence for increased vascular conversion of arachidonic acid to prostacyclin in the two-kidney hypertensive model. The effect of cyclo-oxygenase inhibition on development of hypertension in one- and two-kidney Goldblatt rats was also studied by treating them daily with aspirin (200 mg/kg orally) from 3 days before until 3 weeks after clipping the renal artery. Aspirin-treated two-kidney rats developed significantly higher blood pressures than vehicle-treated controls, but the blood pressures of aspirin-treated one-kidney rats increased less after clipping than those of vehicle-treated controls. It appears paradoxical that transformation of arachidonic acid to prostacyclin is increased, while aspirin has a blood pressure lowering effect in one-kidney Goldblatt rats. It is suggested that there might be a more fundamental disturbance in arachidonate metabolism in hypertension which might contribute to increased vascular reactivity.