title: Dehydroepiandrosterone sulfate induces acute vasodilation of porcine coronary arteries in vitro and in vivo.
abstract: Although an inverse relationship between dehydroepiandrosterone sulfate (DHEAS) and coronary artery disease has been demonstrated in men, the vascular effects of DHEAS are not well defined. The vasoactive effects of intracoronary DHEAS and testosterone (0.1 nM to 1 microM) were examined in vivo in 24 pigs. Epicardial cross-sectional area was measured by intravascular ultrasound, and coronary flow velocity by intravascular Doppler velocimetry. We also examined the effects of antagonism of the androgen receptor, nitric oxide synthase, and potassium channels on DHEAS-induced vasodilation in vitro in coronary rings from male and female pig hearts. DHEAS and testosterone induced increases in cross-sectional area, average peak velocity, and coronary blood flow. The maximal increase in coronary blood flow in response to testosterone was 1.26-fold (P=0.02), and in average peak velocity 1.43-fold (P=0.05), greater than that to DHEAS, whereas increases in cross-sectional area were similar. Vasodilation to both hormones was rapid, with maximal responses occurring <10 minutes after administration. In vitro, DHEAS and testosterone induced vasodilation in coronary rings, greater with testosterone. At doses of 0.1 and 1 microM, the vasodilator effects of DHEAS and testosterone were inhibited by the androgen receptor antagonist flutamide but not the estrogen receptor antagonist ICI 182,780. At 10 microM, neither DHEAS- nor testosterone-induced vasorelaxation was inhibited by flutamide, ICI 182,780, L-NAME, or deendothelialization, but both were attenuated by pretreatment with glibenclamide. No gender differences were observed in any of the responses examined. In conclusion, DHEAS is an acute coronary artery vasodilator, but less potent than testosterone. Its effect might be mediated via androgen receptors and may involve ATP-sensitive potassium channels.
authors.affiliation: Vascular Research Laboratory, Division of Cardiology, University of California, San Francisco, California, USA.
authors.forename: Stuart J
authors.initials: SJ
authors.lastname: Hutchison
authors.forename: Amanda E M
authors.initials: AE
authors.lastname: Browne
authors.forename: Eitetsu
authors.initials: E
authors.lastname: Ko
authors.forename: Tony M
authors.initials: TM
authors.lastname: Chou
authors.forename: Christian
authors.initials: C
authors.lastname: Zellner
authors.forename: Paul A
authors.initials: PA
authors.lastname: Komesaroff
authors.forename: Kanu
authors.initials: K
authors.lastname: Chatterjee
authors.forename: Krishnankutty
authors.initials: K
authors.lastname: Sudhir
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000187:drug effects; D000726:Androgen Antagonists / Q000494:pharmacology; D000818:Animals; D003326:Coronary Circulation / Q000187:drug effects; D003331:Coronary Vessels / Q000000981:diagnostic imaging / Q000187:drug effects*; D019314:Dehydroepiandrosterone Sulfate / Q000494:pharmacology*; D015150:Echocardiography, Doppler; D004730:Endothelium, Vascular / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004958:Estradiol / Q000031:analogs & derivatives / Q000494:pharmacology; D005260:Female; D005485:Flutamide / Q000494:pharmacology; D000077267:Fulvestrant; D005905:Glyburide / Q000494:pharmacology; D006439:Hemodynamics / Q000187:drug effects; D066298:In Vitro Techniques; D054086:KATP Channels; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D010496:Pericardium / Q000187:drug effects; D026902:Potassium Channel Blockers / Q000494:pharmacology; D024661:Potassium Channels, Inwardly Rectifying / Q000187:drug effects; D012727:Sex Characteristics; D013552:Swine; D013739:Testosterone / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects*
chemical_list: D018528:ATP-Binding Cassette Transporters; D000726:Androgen Antagonists; D004791:Enzyme Inhibitors; D054086:KATP Channels; D026902:Potassium Channel Blockers; D024661:Potassium Channels, Inwardly Rectifying; C092520:uK-ATP-1 potassium channel; D000077267:Fulvestrant; D013739:Testosterone; D004958:Estradiol; D019314:Dehydroepiandrosterone Sulfate; D005485:Flutamide; D005905:Glyburide; D019331:NG-Nitroarginine Methyl Ester