5-6-dihydroprostacyclin and Hypertension

This study was designed to examine the contribution of lipoxygenase products to mechanisms of vascular contraction and elevated blood pressure in rats with aortic coarctation-induced hypertension. In cytosolic fractions of aortae taken from hypertensive rats, 12-lipoxygenase protein was increased as compared to normotensive controls. Aortic rings from hypertensive, but not from normotensive rats, exhibited a basal tone which was reduced 74+/-12 and 71+/-22%, respectively, by the lipoxygenase inhibitors cinnamyl-3,4-dihydroxy-alpha-cyanocinnamate (CDC, 10(-5) mol/L) and 5,8,11-eicosatriynoic acid (ETI, 10(-5) mol/L). CDC (8 mg/kg s.c.) did not affect the blood pressure of normotensive rats but decreased that of hypertensive rats from 182+/-6 to 151+/-10 mm Hg. The blood pressure lowering effect of CDC was blunted in hypertensive rats pretreated with indomethacin or antibodies against 5,6-dihydro-prostaglandin I2. These data suggest contribution of lipoxygenase-derived products to mechanisms underlying aortic smooth muscle basal tone and elevated blood pressure in rats with aortic coarctation-induced hypertension. The vasodepressor effect of CDC depends on a mechanism involving vasodilatory prostaglandins.

Topics: 12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; 8,11,14-Eicosatrienoic Acid; Animals; Aorta, Thoracic; Blood Pressure; Caffeic Acids; Cyclooxygenase Inhibitors; Disease Models, Animal; Epoprostenol; Hypertension; Indomethacin; Leukotrienes; Lipoxygenase; Lipoxygenase Inhibitors; Male; Muscle, Smooth, Vascular; Prostaglandins, Synthetic; Rats; Rats, Sprague-Dawley; Vasoconstriction; Vasoconstrictor Agents

Immunoglobulins raised against 5,6-dihydro PGI2 crossreact with PGI2. When infused in vivo into the rat, these immunoglobulins are capable of 1) neutralising the vasodepressor effects (bolus or continuous infusion) of exogenous PGI2, 2) blocking the catabolism of exogenous 3H-PGI2 and prolonging its life-time in the circulation (t 1/2 approx 60 min) while that of 3H-PGE2 is unaffected, 3) trapping an endogenously produced substance which after extraction from blood and dissociation from the ligand-antibody complex, is immunoreactive with 6-keto PGF1 alpha-specific antiserum. Yet the anti-5,6-dihydro PGI2 immunoglobulins have no effect on resting arterial blood pressure both in the normotensive and spontaneously hypertensive rat. These experiments indicate that endogenously produced PGI2 does not play a significant systemic role in blood pressure control although in combination with other vasodilators it could still participate in the regulation of vascular tone at a local level.

Topics: Angiotensin II; Animals; Antibodies; Blood Pressure; Epoprostenol; Hypertension; Norepinephrine; Prostaglandins; Prostaglandins E; Rats