Cyclooxygenase inhibition potentiates the renal vascular response to endothelin-1 in humans

Vascular endothelin-receptor stimulation resultsin vasoconstriction and concomitant production of the vasodilatorsprostaglandin I₂ and nitric oxide.The vascular effects of cyclooxygenase (COx) blockade (diclofenacintravenously) and the subsequent vasoconstrictor response toendothelin-1 (ET-1) infusion 30 min after diclofenac were studied inhealthy men. With COx blockade, cardiac output (7%) and splanchnic(14%) and renal (12%) blood flows fell (all P < 0.001). Splanchnic blood flowreturned to basal value within 30 min. Mean arterial blood pressureincreased (4%, P < 0.001). Splanchnic glucose output fell (22%,P < 0.01). Subsequent ET-1 infusioncaused, compared with previous ET-1 infusion without COx blockade (G. Ahlborg, E. Weitzberg, and J. M. Lundberg. J. Appl.Physiol. 77: 121-126, 1994; E. Weitzberg, G. Ahlborg, and J. M. Lundberg. Biochem. Biophys. Res.Commun. 180: 1298-1303, 1991; E. Weitzberg, G. Ahlborg, and J. M. Lundberg. Clin.Physiol. (Colch.) 13: 653-662, 1993),the same increase in mean arterial blood pressure (4%), decreases incardiac output (13%) and splanchnic blood flow (38%), but nosignificant change in splanchnic glucose output. Renal blood flowreduction was potentiated (33 ± 3 vs. 23 ± 2%,P < 0.02), with a total reductioncorresponding to 43 ± 3%(P < 0.01 vs. 23 ± 3%). Weconclude that COx inhibition induces renal and splanchnicvasoconstriction. The selectively increased renal vascularresponsiveness to ET-1 emphasizes the importance of endogenousarachidonic acid metabolites (i.e., prostaglandin I₂) to counteract ET-1-mediatedrenal vasoconstriction.