Pharmacological characterization of the mechanisms involved in the vasorelaxation induced by progesterone and 17β-estradiol on isolated canine basilar and internal carotid arteries |
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| Institution: | 1. Division of Physiology, Kyushu Dental University, 2-6-1 Manazuru, Kokurakita-ku, Kitakyushu, Fukuoka 803-8580, Japan;2. Department of Oral Diagnostic Science, Nihon University School of Dentistry, 1-8-13 Kandasurugadai, Chiyoda-ku, Tokyo 101-8310, Japan;3. Division of Oral Health Science, Dental Research Center, Nihon University School of Dentistry, 1-8-13 Kanda-Surugadai, Chiyoda-ku, Tokyo 101-8310, Japan;4. Department of Physiology, Nihon University School of Dentistry, 1-8-13 Kandasurugadai, Chiyoda-ku, 101-8310, Japan;5. Division of Functional Morphology, Dental Research Center, Nihon University School of Dentistry, 1-8-13 Kandasurugadai, Chiyoda-ku, Tokyo 101-8310, Japan;1. Resident, Department of Oral Medicine, University of Pennsylvania School of Dental Medicine, Philadelphia, PA, USA;2. Professor, Department of Oral Medicine, University of Pennsylvania School of Dental Medicine, Philadelphia, PA, USA;3. Associate Professor, Department of Oral Medicine, University of Pennsylvania School of Dental Medicine, Philadelphia, PA, USA;1. Department of Neurosurgery, National Hospital Organization, Mito Medical Center, 280 Sakuranosato, Ibaraki-machi, Higashiibaraki, Ibaraki 311-3193, Japan;2. Department of Neurosurgery, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575, Japan;1. Department of Neurosurgery, Keio University School of Medicine, Tokyo, Japan;2. Department of Diagnostic Radiology, Keio University School of Medicine, Tokyo, Japan;3. Department of Neurosurgery, Clemens Hospital, Academic Hospital of Münster University, Münster, Germany;1. Facultad de Ciencias Químicas, Universidad Autónoma de Coahuila, Boulevard Venustiano Carranza esquina con Ing. José Cárdenas Valdés, Colonia República, Saltillo, Coahuila C.P. 25280, México;2. Departamento de Farmacobiología, Cinvestav-Coapa, Czda. de los Tenorios 235,Col. Granjas?Coapa, Deleg. Tlalpan, C.P. 14330, México D.F., México |
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| Abstract: | Progesterone and 17β-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 17β-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 17β-estradiol on KCl- and/or PGF2α-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 μM) and 17β-estradiol (1.8–180 μM): (1) produced concentration-dependent relaxations of KCl- or PGF2α-pre-contracted arterial rings; (2) the relaxations were unaffected by actinomycin D (10 μM), cycloheximide (10 μM), SQ 22,536 (100 μM) or ODQ (30 μM), potassium channel blockers and ICI 182,780 (only for 17β-estradiol). In the basilar artery the vasorelaxation induced by 17β-estradiol was slightly blocked by tetraethylammonium (10 mM) and glibenclamide (KATP; 10 μM). In both arteries, progesterone (10–100 μM), 17β-estradiol (3.1–31 μM) and nifedipine (0.01–1 μM) produced a concentration-dependent blockade of the contraction to CaCl2 (10 μM–10 mM). These results suggest that progesterone and 17β-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 cAMP/cGMP. Potassium channels did not play a role in the relaxation to progesterone in both arteries or in the effect of 17β-estradiol in the internal carotid artery; meanwhile KATP channels play a minor role on the effect of 17β-estradiol in the basilar artery. |
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| Keywords: | Progesterone 17β-Estradiol Vasorelaxation Cerebral arteries |
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