EXPRESSION OF PROSTAGLANDIN H-2-MEDIATED MECHANISM OF VASCULAR CONTRACTION IN HYPERTENSIVE RATS - RELATION TO LIPOXYGENASE AND PROSTACYCLIN SYNTHASE ACTIVITIES

We tested the hypothesis that a prostanoid-mediated mechanism of vascular contraction is expressed in rats with aortic coarctation-induced hypertension. Rings of descending thoracic aorta taken from normotensive and hypertensive rats were contrasted in terms of constrictor responsiveness to arachidonic acid (AA), AA-induced release of eicosanoids, and ability to convert exogenous prostaglandin (PG) H-2 to PGI(2). AA (10(-8) to 10(-5) mol/L) increased isometric tension in aortic rings (bathed in Krebs' bicarbonate buffer) of hypertensive but not normotensive rats. AA (10(-5) mol/L) also elicited the release of PGI(2), PGE(2), thromboxane (TX) A(2), and monohydroxyeicosatetraenoic acids (HETEs); this release from the aortic rings of hypertensive rats exceeded the corresponding release from the aortic rings of normotensive rats. However, the rate of conversion of exogenous PGH(2) to PGI(2) by aortic rings of hypertensive rats was <50% the rate of conversion by aortic rings of normotensive rats. The constrictor effect of AA in aortic rings of hypertensive rats was abolished by an inhibitor of cyclooxygenase (indomethacin, 10 mu mol/L) and a blocker of TXA(2)-PGH(2) receptors (SQ29548, 1 mu mol/L) but was not affected by an inhibitor of TXA(2) synthesis (CGS13080, 10 mu mol/L), suggesting mediation by PGH(2). The lipoxygenase inhibitor baicalein (75 mu mol/L) also attenuated the constrictor effect of AA in aortic rings of hypertensive rats while decreasing the associated release of HETEs and correcting the impairment in the conversion of PGH(2) to PGI(2). We conclude that the expression of AA-induced PGH(2)-mediated constriction of aortic rings is increased in hypertensive rats because of increased PGH(2) formation associated with disruption in the coupling of PGH(2) synthesis to PGH, metabolism caused by a product(s) of lipoxygenase with the ability to inhibit prostacyclin synthase.