Contractile responses to Bay K 8644 in rats with coarctation-induced hypertension

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.