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, 45 Ca 2ϩ 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 -ERs that were slightly reduced in aging rats. In endothelium-intact vascular strips, phenylephrine (Phe; 10 Ϫ5 mol/L) caused greater active stress in aging rats (9.3Ϯ0.2) than in adult rats (6.2Ϯ0.3ϫ10 4 N/m 2 ). 17-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 Ca 2ϩ influx, produced greater active stress in aging rats (9.1Ϯ0.3) than in adult rats (5. 9Ϯ0.2ϫ10 4 N/m 2 ). E2 caused relaxation of KCl contraction and inhibition of Phe-and KCl-induced 45 Ca 2ϩ 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 Ca 2ϩ 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.
Abstract-Endothelin-1 (ET-1) has been implicated in coronary vasospasm by enhancing coronary vasoconstriction to vasoactive eicosanoids, and a role for protein kinase C (PKC) activation has been suggested. However, the cellular mechanisms downstream from PKC activation are unclear. We investigated whether physiological concentrations of ET-1 enhance coronary smooth muscle contraction by activating a PKC-mediated signaling pathway involving tyrosine phosphorylation and activation of mitogen-activated protein kinase (MAPK). Cell contraction was measured in smooth muscle cells isolated from porcine coronary artery, [Ca 2ϩ ] i was measured in fura-2 loaded cells, and tissue fractions were examined for reactivity with anti-phosphotyrosine (P-Tyr) and anti-MAPK antibodies using immunoprecipitation and immunoblot analysis. In Hanks
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