The role of eicosanoids in angiotensin-dependent hypertension

Many eicosanoids produced in vascular and renal structures are endowed with the ability to influence vascular and renal mechanisms of blood pressure regulation. Eicosanoids subserve both prohypertensive and antihypertensive mechanisms. The development of angiotensin-dependent hypertension in rats is accompanied by increased vascular production of thromboxane A(2) (TXA(2)) and of lipoxygenase-derived products with the ability to inhibit prostacyclin synthase. As a result of these abnormalities, the activity of presser mechanisms mediated by TXA(2) and/or prostaglandin (PG) H-2 is increased. The cancellation of TXA(2)- and/or of PGH(2)-mediated presser mechanisms, after treatment with thromboxane synthase inhibitors or TXA(2)/PGH(2) receptor blockers, lowers blood pressure in rats with angiotensin-dependent hypertension. Inhibitors of lipoxygenase also lower blood pressure in such animals, in part by decreasing the synthesis of lipoxygenase-derived inhibitors of prostacyclin synthase. Thus, the vasodepressor effect of these agents is accompanied by increased vascular formation of PGI(2) and can be prevented by cyclooxygenase inhibitors. Cyclooxygenase-derived eicosanoids, PGE(2) and PGI(2), also subserve antihypertensive mechanisms in angiotensin-dependent models of hypertension. The level of blood pressure in such models of hypertension reflects, in part, the interplay among prohypertensive and antihypertensive functions subserved by cyclooxygenase- and lipoxygenase-derived eicosanoids.