Role of COX-2-derived metabolites in regulation of the renal hemodynamic response to norepinephrine

derived metabolites in regulation of the renal hemodynamic response to norepinephrine. Am J Physiol Renal Physiol 281: F975–F982, 2001.—The objective of this study was to examine the role of cylcooxygenase (COX)-2-derived prostaglandins (PG) in modulating the renal hemodynamic effects of norepinephrine (NE) during low or normal sodium intake. The relative contri-bution of each COX isoform in producing the PG that attenuate the renal NE effects during normal sodium intake was also evaluated. The renal response to three doses of NE (50, 100, and 250 ngzkg21zmin21) was evaluated in anesthetized dogs pre-treated with vehicle, a selective COX-2 inhibitor (nimesulide), or a nonselective COX inhibitor (meclofenamate). Intrarenal infusion of the two lower doses of NE in vehicle-pretreated dogs with normal sodium intake (n 5 8) elicited an increase in renal vascular resistance (RVR; 21 and 34%) without inducin