title: Age-related reduction in estrogen receptor-mediated mechanisms of vascular relaxation in female spontaneously hypertensive rats.
abstract: Hypertension increases with aging, and changes in vascular estrogen receptors (ERs) may play a role in age-related hypertension in women. We tested whether age-related increases in blood pressure in female spontaneously hypertensive rats (SHRs) are associated with reduction in amount and/or vascular relaxation effects of estrogen and ER. Arterial pressure and plasma estradiol were measured in adult (12 weeks) and aging (16 months) female SHRs, and thoracic aorta was isolated for measurement of active stress, 45Ca2+ influx, and ERs. Arterial pressure was greater and plasma estradiol was less in aging females than in adult females. In aorta of adult females, Western blots revealed alpha- and beta-ERs that were slightly reduced in aging rats. In endothelium-intact vascular strips, phenylephrine (Phe; 10(-5) mol/L) caused greater active stress in aging rats (9.3+/-0.2) than in adult rats (6.2+/-0.3x10(4) N/m2). 17beta-estradiol (E2) caused relaxation of Phe contraction and stimulation of vascular nitrite/nitrate production, which was reduced in aging rats. In endothelium-denuded strips, E2 still caused relaxation of Phe contraction, which was smaller in aging rats than adult rats. KCl (51 mmol/L), which stimulates Ca2+ influx, produced greater active stress in aging rats (9.1+/-0.3) than in adult rats (5.9+/-0.2x10(4) N/m2). E2 caused relaxation of KCl contraction and inhibition of Phe- and KCl-induced 45Ca2+ influx, which were reduced in aging rats. Thus, aging in female SHR is associated with reduction in ER-mediated NO production from endothelial cells and decrease in inhibitory effects of estrogen on Ca2+ entry mechanisms of smooth muscle contraction. The age-related decrease in ER-mediated vascular relaxation may explain the increased vascular contraction and arterial pressure associated with aging in females.
authors.affiliation: Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, USA.
authors.forename: Fanisha L
authors.initials: FL
authors.lastname: Wynne
authors.forename: Jason A
authors.initials: JA
authors.lastname: Payne
authors.forename: Ashley E
authors.initials: AE
authors.lastname: Cain
authors.forename: Jane F
authors.initials: JF
authors.lastname: Reckelhoff
authors.forename: Raouf A
authors.initials: RA
authors.lastname: Khalil
mesh_terms: D000367:Age Factors; D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D001794:Blood Pressure; D002118:Calcium / Q000378:metabolism; D046508:Culture Techniques; D006152:Cyclic GMP / Q000378:metabolism; D004730:Endothelium, Vascular / Q000503:physiopathology; D004958:Estradiol / Q000097:blood / Q000494:pharmacology*; D005260:Female; D006973:Hypertension / Q000097:blood / Q000378:metabolism / Q000503:physiopathology*; D009119:Muscle Contraction; D009131:Muscle, Smooth, Vascular / Q000503:physiopathology; D009569:Nitric Oxide / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR; D011960:Receptors, Estrogen / Q000378:metabolism*; D014664:Vasodilation
chemical_list: D011960:Receptors, Estrogen; D009569:Nitric Oxide; D004958:Estradiol; D006152:Cyclic GMP; D002118:Calcium