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

Progesterone and 17 beta-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 17 beta-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 17 beta-estradiol on KCl- and/or PGF(2 alpha)-pre-contracted arterial rings were investigated in absence or presence of several antagonists/inhibitors/blockers; the effect on the contractile responses to CaCl2 was also determined. In both arteries progesterone (5.6-180 mu M) and 17 beta-estradiol (1.8-180 mu M): (1) produced concentration-dependent relaxations of KCl- or PGF(2 alpha)-pre-contracted arterial rings; (2) the relaxations were unaffected by actinomycin D (10 mu M), cycloheximide (10 mu M), SQ 22,536 (100 mu M) or ODQ (30 mu M), potassium channel blockers and ICI 182,780 (only for 17 beta-estradiol). In the basilar artery the vasorelaxation induced by 17 beta-estradiol was slightly blocked by tetraethylammonium (10 mM) and glibenclamide (K-ATP; 10 mu M). In both arteries, progesterone (10-100 mu M), 17 beta-estradiol (3.1-31 mu M) and nifedipine (0.01-1 mu M) produced a concentration-dependent blockade of the contraction to CaCl2 (10 mu M-10 mM). These results suggest that progesterone and 17 beta-estradiol produced relaxation in the basilar and internal carotid arteries by blockade of L-type voltage dependent Ca2+ channel but not by genomic mechanisms or production of cANIP/cGMP. Potassium channels did not play a role in the relaxation to progesterone in both arteries or in the effect of 17 beta-estradiol in the internal carotid artery; meanwhile K-ATP channels play a minor role on the effect of 17 beta-estradiol in the basilar artery. (C) 2014 Elsevier Inc. All rights reserved.