Maintenance of normal agonist-induced endothelium-dependent relaxation in uraemic and hypertensive resistance vessels

Background. The nitric oxide system has been implicated in several diseases with vascular complications including diabetes mellitus and hypertension. Despite the high prevalence of hypertension and cardiovascular complication s in renal failure few studies have examined vascular and endothelial funct ion in uraemia. We therefore chose to study possible abnormalities of the n itric oxide vasodilator system in an animal model of chronic renal failure. Methods. Adult spontaneous hypertensive rats and Wistar Kyoto rats were sub jected to a 5/6 nephrectomy with control animals having sham operations. Af ter 4 weeks blood pressure was recorded and the animals were sacrificed. Br anches of the mesenteric arteries were isolated and mounted on a Mulvany my ograph. All experiments were performed in the presence of indomethacin(10(- 5) M). The vessels were first preconstricted with noradrenaline, exposed to increasing concentrations of acetylcholine (10(-8) to 10(-4) M) and subseq uently to sodium nitroprusside (10(-5) M). Results. There was no difference in the relaxation of the four groups of ve ssels to any of the concentrations of acetylcholine used nor was there any significant difference in the EC(50)s (control Wistar Kyoto 6.1 +/- 1.4 x 1 0(-8) M; uraemic Wistar Kyoto 5.4 +/- 0.8 x 10(-8) M; control spontaneous h ypertensive rats 4.5 +/- 0.6 x 10(-8) M; uraemic spontaneous hypertensive r ats 6 +/- 0.7 x 10(-8) M). Vasodilatation in response to sodium nitroprussi de was unchanged in uraemic vessels. In addition the vascular responses to both acetylcholine and sodium nitroprusside were unaltered in spontaneous h ypertensive rats. Conclusions. We conclude that normal agonist-induced endothelium-dependent relaxation is maintained in experimental uraemia and hypertension.