Pharmacological characterization of the mechanisms involved in the vasorelaxation induced by progesterone and 17p?estradiol on isolated canine basilar and internal carotid arteries

摘要

Progesterone and 17beta-estradiol induce vasorelaxation through non-genomic mechanisms in several isolated blood vessels; however, no study has systematically evaluated the mechanisms involved in the relaxation induced by 17beta-estradiol and progesterone in the canine basilar and internal carotid arteries that play a key role in cerebral circulation. Thus, relaxant effects of progesterone and 17beta-estradiol on KG- and/or PGF_(2alpha)-pre-contracted arterial rings were investigated in absence or presence of several antagonists/inhibitors/blockers; the effect on the contractile responses to CaCl_2 was also determined. In both arteries progesterone (5.6-180 muM) and 17beta-estradiol (1.8-180muM): (1) produced concentration-dependent relaxations of KG- or PGF_(2alpha)-pre-contracted arterial rings; (2) the relaxations were unaffected by actinomycin D (10 muM), cycloheximide (10 uM), SQ 22,536 (100 uM) or ODQ.(30 muM), potassium channel blockers and ICI 182,780 (only for 17beta-estradiol). In the basilar artery the vasorelaxation induced by 17beta-estradiol was slightly blocked by tetraethylammonium (10 muM) and glibenclamide (K_(ATp); 10muM). In both arteries, progesterone (10-100 uM), 17beta-estradiol (3.1-31 muM) and nifedipine (0.01-1 muM) produced a concentration-dependent blockade of the contraction to CaCl_2 (10 muM-10 muM). These results suggest that progesterone and 17p-estradiol produced relaxation in the basilar and internal carotid arteries by blockade of L-type voltage dependent Ca~(2+) channel but not by genomic mechanisms or production of cAMP/cGMP. Potassium channels did not play a role in the relaxation to progesterone in both arteries or in the effect of 17beta~estradiol in the internal carotid artery; meanwhile K_(ATP) channels play a minor role on the effect of 17p-estradiol in the basilar artery.