title: Contractile responses to Bay K 8644 in rats with coarctation-induced hypertension.
abstract: This study examines potential-operated calcium channel function in rats made hypertensive by aortic coarctation. The hypothesis that channel function is influenced by elevated arterial pressure was tested by comparing contractile responses to elevated K+ and to the potential-operated calcium channel agonist, Bay K 8644, in aortic segments above (thoracic) and below (abdominal) the coarctation that are exposed to hypertensive and normotensive pressures, respectively. To control for vessel differences, the effects of Bay K 8644 were also examined in abdominal aortae from two-kidney, one-clip hypertensive rats. Sensitivity to K+ (EC15) was significantly greater in both thoracic and abdominal aortae from coarctation-hypertensive rats than in those from normotensive sham rats. In the thoracic aorta, maximal contractile response to Bay K 8644 (normalized to contraction produced by 100 mM K+) was significantly greater in coarctation-hypertensive rats (124 +/- 9%) than in sham rats (12 +/- 6%). However, Bay K 8644 did not elicit contraction in abdominal aortae from either group. When [K+]o was increased (19.2 mM), thoracic aortae from coarctation-hypertensive rats were more sensitive to Bay K 8644, but there were no differences in maximal responses among thoracic and abdominal aortae. Bay K 8644 evoked dose-dependent contraction in all abdominal aortic strips from two-kidney, one-clip hypertensive rats (maximum = 68 +/- 11%). In summary, vascular responsiveness to Bay K 8644 is increased in the thoracic but not abdominal aorta from coarctation-hypertensive rats, whereas sensitivity to elevated K+ is increased in both vessels. Enhanced K+ sensitivity in the abdominal aorta may be related to general effects of the cation on membrane potential. However, augmented responsiveness to Bay K 8644 suggests a specific alteration in the function of potential-operated calcium channels that is dependent upon elevated blood pressure and is not due to differences in responsiveness between the thoracic and abdominal aortae.
authors.affiliation: Department of Physiology, University of Michigan Medical School, Ann Arbor 48109-0622.
authors.forename: D S
authors.initials: DS
authors.lastname: Storm
authors.forename: R C
authors.initials: RC
authors.lastname: Webb
mesh_terms: D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology*; D000818:Animals; D001012:Aorta, Abdominal / Q000187:drug effects / Q000502:physiology / Q000503:physiopathology*; D001013:Aorta, Thoracic / Q000187:drug effects / Q000502:physiology / Q000503:physiopathology*; D001017:Aortic Coarctation / Q000503:physiopathology*; D004305:Dose-Response Relationship, Drug; D006978:Hypertension, Renovascular / Q000503:physiopathology*; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology / Q000503:physiopathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012016:Reference Values; D012077:Renal Artery
chemical_list: D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester