Objective: The present study was designed to analyse whether hypertension alters the involvement of cyclooxygenase-2-derived mediators in phenylephrine-induced vasoconstrictor responses.
Methods: Vascular reactivity experiments were performed in aortic segments from normotensive, Wistar-Kyoto, and spontaneously hypertensive rats (SHR); protein expression was measured by western blot and/or immunohistochemistry, and prostaglandin F2alpha (PGF2alpha), 8-isoprostane and prostacyclin release were determined by enzyme immunoassay commercial kits.
Results: The protein synthesis inhibitor dexamethasone (1 micromol/l), the non-selective cyclooxygenase inhibitor indomethacin (10 micromol/l), the selective cyclooxygenase-2 inhibitor NS 398 (1 micromol/l), and the thromboxane A2/prostaglandin H2 (TP) receptor antagonist SQ 29,548 (1 micromol/l), reduced the concentration-response curves to phenylephrine more in segments from hypertensive than from normotensive rats; however, the thromboxane A2 (TxA2) synthase inhibitors furegrelate (10 micromol/l) and OKY 046 (1 and 10 micromol/l) had no effect in either strain. Removing endothelium or adding dexamethasone almost abolished the NS 398 effect. Cyclooxygenase-2 protein expression, which was reduced by dexamethasone, was higher in aorta from hypertensive animals. In both strains cyclooxygenase-2 was localized mainly in endothelial cells and adventitial fibroblasts. 13,14-Dihydro-15-keto-PGF2alpha, 6-keto-PGF1alpha and 8-isoprostane levels were greater in the medium from hypertensive than from normotensive rats; NS 398 decreased levels of the three metabolites studied only in the medium from SHR.
Conclusions: PGF2alpha and 8-isoprostane seem to be involved in the response to phenylephrine in rat aorta; this involvement is greater in hypertensive rats, probably due to a higher endothelial induction of cyclooxygenase-2.