Effect of chronic high pressure on transient and tonic vascular contractions to serotonin in hypertension

Abstract

This study examined whether vascular contractions related to the extracellular or intracellular pools of calcium activated by serotonin are altered by high arterial pressure in chronic hypertension. Coarctation hypertensive (CH), sham normotensive control (C), and one-kidney, one-clip hypertensive rats (1K1C) were used. Tail systolic, carotid, and femoral arterial pressures were measured. Thoracic aortas from 1K1C and CH rats, as well as abdominal aortas from 1K1C rats, but not abdominal aortas from CH rats were exposed chronically to elevated arterial pressure. Isolated rings of thoracic and abdominal aortas from all groups were suspended in muscle baths for isometric force recordings. After cellular calcium depletion, dose-response curves to extracellular calcium, in the presence of 10(-5) mol/L serotonin, were unchanged in thoracic or abdominal aortas among the three groups. In the presence of submaximum levels of serotonin (2 x 10(-6) mol/L), thoracic and abdominal rings without endothelium and abdominal rings with endothelium from the three groups showed similar responses to extracellular calcium. Such responses were significantly depressed in thoracic rings with endothelium from CH and 1K1C rats. Transient contractions attributable to release of an intracellular calcium pool by 10(-5) mol/L serotonin were enhanced significantly in hypertensive thoracic and abdominal aortas from 1K1C rats, when the pool was loaded with 0.25, 0.5, 1.0, 2.0, or 4.0 mmol/L CaCl2, as well as in hypertensive thoracic aortas from CH rats when the pool was loaded with 1.0, 2.0, or 4.0 mmol/L CaCl2, but not in normotensive abdominal aortas from CH rats at any calcium-loading concentration. Similar results were observed in aortas from C, CH, and 1K1C rats loaded with 1.0 or 2.0 mmol/L CaCl2 and stimulated with 2 x 10(-6) mol/L serotonin. Endothelial removal had no effect on these calcium-release contractions in abdominal aortas from any group, but enhanced contractions in thoracic aortas of 1K1C rats. In rings loaded with 2.0 mmol/L CaCl2, 2-nitro-4-carboxyphenyl-N,N-diphenylcarbamate inhibited contractions attributable to release of cellular calcium stores to a similar extent in C, CH, and 1K1C rats. This study suggests that serotonin-stimulated intracellular calcium-dependent aortic contractions are enhanced by elevated pressure in renal hypertensive rats.