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(Hypertension. 2004;43:405.)
© 2004 American Heart Association, Inc.

Scientific Contribution

Age-Related Reduction in Estrogen Receptor–Mediated Mechanisms of Vascular Relaxation in Female Spontaneously Hypertensive Rats

Fanisha L. Wynne; Jason A. Payne; Ashley E. Cain; Jane F. Reckelhoff; Raouf A. Khalil

From the Department of Physiology and Biophysics, University of Mississippi Medical Center (F.L.W., J.A.P., A.E.C., J.F.R.), Jackson; Research and Development, Veterans Affairs Medical Center (R.A.K.), West Roxbury, Mass; Department of Medicine, Harvard Medical School (R.A.K.), Boston, Mass.

Correspondence to Raouf A. Khalil, MD, PhD, Harvard Medical School, VA Boston Healthcare - Research, 1400 VFW Parkway, 3/2B123, Boston, MA 02132. E-mail raouf_khalil{at}hms.harvard.edu

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 - and ß-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±0.3x10⁴ N/m²). 17ß-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±0.2x10⁴ 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.

Key Words: hormones • endothelium • muscle, smooth, vascular • calcium

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