The Blood Pressure-Lowering Effect of 20-HETE Blockade in Cyp4a14(-/-) Mice Is Associated with Natriuresis.

摘要: 20-Hydroxy-5,8,11,14-eicosatetraenoic acid (20-HETE) has been linked to pro-hypertensive and anti-hypertensive actions through its ability promote vasoconstriction inhibit Na transport in the ascending limb of loop Henle, respectively. In this study, we assessed effects 20-HETE blockade on blood pressure, renal hemodynamics, urinary sodium excretion Cyp4a14(−/−) male mice, which display androgen-driven 20-HETE–dependent hypertension. Administration 2,5,8,11,14,17-hexaoxanonadecan-19-yl 20-hydroxyicosa-6(Z),15(Z)-dienoate (20-SOLA), a water-soluble antagonist, drinking water normalized pressure hypertensive mice (±124 vs. ±153 mmHg) while having no effect age-matched normotensive wild-type (WT) mice. Hypertension was accompanied by decreased perfusion reduced glomerular filtration rates, were corrected treatment with 20-SOLA. Interestingly, treated 20-SOLA displayed increased that paralleled reduction suggestive an antinatriuretic activity endogenous This interpretation is line observation natriuretic response acute isotonic saline loading significantly impaired relative WT mice; impairment treatment. Hence, appears conservation presumably, as result associated changes hemodynamics and/or direct stimulatory action tubular reabsorption.