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

Vascular endothelin-receptor stimulation results in vasoconstriction and concomitant production of the vasodilators prostaglandin I2 and nitric oxide. The vascular effects of cyclooxygenase (COx) blockade (diclofenac intravenously) and the subsequent vasoconstrictor response to endothelin-1 (ET-1) infusion 30 min after diclofenac were studied in healthy men. With COx blockade, cardiac output (7%) and splanchnic (14%) and renal (12%) blood flows fell (all P < 0.001). Splanchnic blood flow returned to basal value within 30 min. Mean arterial blood pressure increased (4%, P < 0.001). Splanchnic glucose output fell (22%, P < 0.01). Subsequent ET-1 infusion caused, 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 in cardiac output (13%) and splanchnic blood flow (38%), but no significant change in splanchnic glucose output. Renal blood flow reduction was potentiated (33 +/- 3 vs. 23 +/- 2%, P < 0.02), with a total reduction corresponding to 43 +/- 3% (P < 0.01 vs. 23 +/- 3%). We conclude that COx inhibition induces renal and splanchnic vasoconstriction. The selectively increased renal vascular responsiveness to ET-1 emphasizes the importance of endogenous arachidonic acid metabolites (i.e., prostaglandin I2) to counteract ET-1-mediated renal vasoconstriction.