Effect of 17-beta estradiol in the rabbit: Endothelium-dependent and -independent mechanisms of vascular relaxation

被引:0
作者
Ma, LM
Robinson, CP
Thadani, U
Patterson, E
机构
[1] UNIV OKLAHOMA, HLTH SCI CTR, COLL MED, DEPT PHARMACOL, OKLAHOMA CITY, OK 73190 USA
[2] UNIV OKLAHOMA, HLTH SCI CTR, COLL MED, DEPT MED, OKLAHOMA CITY, OK 73190 USA
[3] UNIV OKLAHOMA, HLTH SCI CTR, COLL PHARM, DEPT PHARMACOL & TOXICOL, OKLAHOMA CITY, OK 73190 USA
关键词
17; beta-estradiol; nitric oxide; vasodilation;
D O I
暂无
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Short-term estrogen administration has been independently proposed to produce arterial vasodilation by both an indirect mechanism and a direct mechanism (inhibition of calcium entry though the L-type calcium channel). The proposed contributions of such diverse mechanisms to the vascular actions of 17 beta-estradiol were examined in perfused hearts and in aortic ring sections isolated from female rabbits. In isolated rabbit hearts retrogradely perfused with Tyrode's solution, concentration-response curves to 17 beta-estradiol (10(-9)-10(-5) M) were performed under control conditions and during perfusion with Bay K8644 (10(-7) M). 17 beta-Estradiol produced a concentration-dependent decrease in coronary vascular resistance proportional to nitric oxide (NO) release in the presence and absence of Bay K8644. The addition of N-G-nitro-L-arginine methyl eater (L-NAME; 10(-4) M) to the perfusate (a) completely inhibited NO formation, (b) produced a 2.3-fold and 1.55-fold rightward shift in the concentration-response curve to 17 beta-estradiol for Bay K8644 treated and control hearts, respectively, and (c) failed to prevent coronary artery vasodilation. In isolated aortic rings contracted with Bay K8644, 17 beta-estradiol (10(-5) M) relaxed both intact (58%) and denuded (54%) aortic rings. L-NAME (10(-4) M) completely blocked NO release in intact rings but did not prevent relaxation in denuded aortic rings. The data demonstrate (a) an endothelium-dependent relaxation by 17 beta-estradiol, coincident with NO formation and suppressed by L-NAME, and (b) a direct relaxation of aortic and coronary smooth muscle independent of NO formation at higher 17 beta-estradiol concentrations.
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页码:130 / 135
页数:6
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