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) H2 to PGI2. AA (10`8 to 10`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 PGI2, PGE2, thromboxane (TX) A2, 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 PGH2 to PGI2 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 hromboxane (TX) A2 and prostaglandin (PG) H2 stimulate contraction of vascular smooth muscle via interaction with a common receptor.1 Treatment with a blocker of TXA2-PGH2 receptors lowers the blood pressure of rats with established angiotensin II-and salt-induced hypertension2 and of rats in the early stage of the hypertension produced by complete ligation of the aorta between the renal arteries,3 a model of angiotensin-dependent hypertension. A blocker of TXA2-PGH2 receptors also was found to attenuate the constrictor effect of angiotensin II and calcium ionophore A23187 in rings of thoracic aorta taken from rats with aortic coarctation-induced hypertension but not from normotensive rats.45 From these findings, it was inferred that a pressor mechanism linked to the activation of TXA2-PGH2 receptors contributes to the increase in blood pressure and vascular contractility in angiotensin-dependent models of hypertension.2 5The present study was designed to investigate whether a prostanoid-mediated mechanism of vascular contraction is hyperexpressed in rats with aortic coarctation-induced hypertension. To inhibitor of cyclooxygenase (indomethacin, 10 gmol/L) and a blocker of TXA2-PGH2 receptors (SQ29548, 1 ,umol/L) but was not affected by an inhibitor of TXA2 synthesis (CGS13080, 10 ,umol/L), suggesting mediation by PGH2. The lipoxygenase inhibitor baicalein (75 ,umol/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 PGH2 to PGI2. We conclude that the expression of AA-induced PGH2-mediated constriction of aortic rings is increased in hypertensive rats because of increased PGH2 formation associated with disruption in the coupling of PGH2 synthesis to PGH2 metabolism caused by a product(s) of lipoxygenase with the ability to inhibit prostacyclin synthase. (Circ Res. 1994;74:197-205.) Key Words * thromboxane-prostaglandi...
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