Soy isoflavones improve endothelial function in spontaneously hypertensive rats. - GreenMedInfo Summary
Soy isoflavones improve endothelial function in spontaneously hypertensive rats in an estrogen-independent manner: role of nitric-oxide synthase, superoxide, and cyclooxygenase metabolites.
Pharmacology. 2003 Jun;68(2):81-8. PMID: 15958720
Department of Pharmacology, School of Pharmacy, University of Granada, Spain.
The aim of this study was to analyze the effects of the isoflavones genistein and daidzein, and the mammalian estrogen 17beta-estradiol on endothelial function in isolated aortic rings from male spontaneously hypertensive rats (SHR) and Wistar Kyoto rats (WKY). Relaxation to acetylcholine on precontracted rings was impaired and endothelium-dependent contraction to acetylcholine in aortic rings was increased in SHR compared with WKY. Aortic NADPH-stimulated O(2)(-) release and prostaglandin (PG)H(2) production evoked by acetylcholine were increased, whereas nitric-oxide synthase activity was reduced in SHR versus WKY. Genistein, daidzein, or 17beta-estradiol enhanced the relaxant response to acetylcholine and decreased the endothelium-dependent vasoconstrictor responses to acetylcholine in SHR, but not in WKY, and these effects were not modified by the estrogen receptor antagonist ICI 182,780 (7alpha,17beta-[9[(4,4,5,5,5-pentafluoropentyl)-sulfinyl]nonyl]estra-1,3,5(10)-triene-3,17-diol). Moreover, isoflavones enhanced nitric-oxide (NO) synthase activity and inhibited NADPH-stimulated O(2)(-) roduction and endothelial release of PGH(2). The contractions induced by the TP receptor agonist U46619 (9,11-dideoxy-11alpha,9alpha-epoxymethanoprostaglandin F(2alpha)) in denuded aortic rings were inhibited by genistein, daidzein, and 17beta-estradiol in both strains. In conclusion, the isoflavones genistein and daidzein and 17beta-estradiol restore endothelial function in male SHR through estrogen receptor-independent mechanisms. Increased NO production and protection of NO from O(2)(-)-driven inactivation might be involved in the improvement of vascular relaxation to acetylcholine in aortic rings from SHR. Moreover, isoflavones and 17beta-estradiol inhibited aortic endothelium-dependent contraction to acetylcholine in SHR by reducing the endothelial PGH(2) release and its vasoconstrictor response.