Vascular smooth muscle responses to endothelial autacoids in rats with chronic coarctation hypertension

Abstract

Objective: To examine whether elevated intravascular pressure in chronic hypertension alters responses of vascular smooth muscle to agents of endothelial origin.

Methods: Coarctation hypertensive, sham normotensive control, and one-kidney, one clip hypertensive (1K1C) rats were used. Tail systolic, carotid and femoral arterial pressures were measured. Responses to histamine, endothelin-1 and the prostacyclin analog iloprost were evaluated in isolated helically cut strips of thoracic and abdominal aortas, with and without endothelium, from all groups. Responses to nitroglycerin were also evaluated in strips of abdominal aortas.

Results: Thoracic aortas from 1K1C and coarctation hypertensive rats, as well as abdominal aortas from 1K1C rats, but not abdominal aortas from coarctation hypertensive rats were exposed chronically to elevated arterial pressure. Endothelium-dependent maximal relaxation by histamine was significantly depressed in thoracic aortas from both groups of rats, as well as in abdominal aortas from 1K1C rats. Maximal relaxation and sensitivity to histamine were normal in abdominal aortas from coarctation hypertensive rats. Sensitivity to nitroglycerin was impaired in abdominal aortas from 1K1C rats but not in those from coarctation hypertensive rats; maximal relaxation to nitroglycerin was similar in all groups. Relaxation to iloprost was independent of the endothelium, observed only in thoracic aortas and impaired in hypertensive rats. Responses to endothelin-1 were similar in the groups.

Conclusion: Vasorelaxation by histamine, iloprost and nitroglycerin are impaired in hypertension. The impaired relaxation by histamine results from exposure of the vascular endothelium to chronically elevated pressure. This impairment may be related to effects of high pressure in reducing the ability of the endothelium to produce endothelium-derived relaxing factor and inhibit cyclic GMP-dilator mechanisms.