title: Aging reduces the responsiveness of coronary arteries from male Wistar rats to the vasodilatory action of testosterone.
abstract: This study was performed to examine whether aging affects the vasodilatory effects of testosterone in the coronary arteries of male rats. Isolated coronary arteries from young mature (3-4 months) and elderly (22-26 months) male Wistar rats were studied in a wire myograph. Contractile function and endothelial function were assessed by measuring vasomotor responses to 10-100 mmol/l KCl, 0.1 mmol/l prostaglandin F(2alpha) (PGF(2alpha)) and 10 micromol/l acetylcholine. Sensitivity to the vasodilatory effects of testosterone was assessed by constructing dose-response curves to concentrations between 1 micromol/l and 1 mmol/l testosterone dissolved in water in vessels maximally preconstricted with PGF(2alpha). The compliance characteristics of each vessel and serum testosterone levels from each animal were measured. Histological sections of myocardium were examined for differences in coronary artery morphology. Vessels from elderly animals were significantly more resistant to the vasodilatory effects of testosterone than vessels from young animals (P=0.001 by analysis of covariance). Vessels from elderly animals were also significantly less compliant (7.32+/-0.43 microm/mN, compared with 10.99+/-1.52 microm/mN in young animals; P=0.011), and the levels of circulating testosterone in elderly animals were lower, but not significantly so (2.04+/-0.63 nmol/l compared with 3.88+/-1.7 nmol/l; P=0.32). Vessels from elderly animals were less contractile in response to KCl than those from young animals (P=0.004 by analysis of covariance). There were no significant differences between the two groups in their responses to PGF(2alpha) or acetylcholine. Thus it is concluded that coronary arteries from elderly rats are significantly less sensitive to the vasodilatory effects of testosterone than those from young animals.
authors.affiliation: Department of Cardiology, Royal Hallamshire Hospital, Glossop Road, Sheffield S10 2JF, UK.
authors.forename: K M
authors.initials: KM
authors.lastname: English
authors.forename: R D
authors.initials: RD
authors.lastname: Jones
authors.forename: T H
authors.initials: TH
authors.lastname: Jones
authors.forename: A H
authors.initials: AH
authors.lastname: Morice
authors.forename: K S
authors.initials: KS
authors.lastname: Channer
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000375:Aging / Q000502:physiology*; D000818:Animals; D003331:Coronary Vessels / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D008297:Male; D011189:Potassium Chloride / Q000494:pharmacology; D011460:Prostaglandins F / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013739:Testosterone / Q000494:pharmacology*; D014664:Vasodilation / Q000187:drug effects*
chemical_list: D011460:Prostaglandins F; D013739:Testosterone; D011189:Potassium Chloride; D000109:Acetylcholine