In:
Hypertension, Ovid Technologies (Wolters Kluwer Health), Vol. 49, No. 6 ( 2007-06), p. 1364-1370
Kurzfassung:
This study investigated the contribution of estrogen receptors (ERs) α and β for epicardial coronary artery function, vascular NO bioactivity, and superoxide (O 2 − ) formation. Porcine coronary rings were suspended in organ chambers and precontracted with prostaglandin F 2α to determine direct effects of the selective ER agonists 4,4′,4″-(4-propyl-[ 1 H]pyrazole-1,3,5-triyl)tris-phenol (PPT) or 2,3-bis(4-hydroxyphenyl)-propionitrile (DPN) or the nonselective ER agonist 17β-estradiol. Indirect effects on contractility to U46619 and relaxation to bradykinin were assessed and effects on NO, nitrite, and O 2 − formation were measured in cultured cells. Within 5 minutes, selective ERα activation by PPT, but not 17β-estradiol or the ERβ agonist DPN, caused rapid, NO-dependent, and endothelium-dependent relaxation (49±5%; P 〈 0.001 versus ethanol). PPT also caused sustained endothelium- and NO-independent vasodilation similar to 17β-estradiol after 60 minutes (72±3%; P 〈 0.001 versus ethanol). DPN induced endothelium-dependent NO-independent relaxation via endothelium-dependent hyperpolarization (40±4%; P 〈 0.01 versus ethanol). 17β-Estradiol and PPT, but not DPN, attenuated the responses to U46619 and bradykinin. All of the ER agonists increased NO and nitrite formation in vascular endothelial but not smooth muscle cells and attenuated vascular smooth muscle cell O 2 − formation ( P 〈 0.001). ERα activation had the most potent effects on both nitrite formation and inhibiting O 2 − ( P 〈 0.05). These data demonstrate novel and differential mechanisms by which ERα and ERβ activation control coronary artery vasoreactivity in males and females and regulate vascular NO and O 2 − formation. The findings indicate that coronary vascular effects of sex hormones differ with regard to affinity to ERα and ERβ, which will contribute to beneficial and adverse effects of hormone replacement therapy.
Materialart:
Online-Ressource
ISSN:
0194-911X
,
1524-4563
DOI:
10.1161/HYPERTENSIONAHA.106.081554
Sprache:
Englisch
Verlag:
Ovid Technologies (Wolters Kluwer Health)
Publikationsdatum:
2007
ZDB Id:
2094210-2
