24-HOUR VARIATIONS IN THE EFFECT OF NITRODILATORS IN RAT AORTA - LACKOF INFLUENCE OF THE ENDOTHELIUM

Time-dependent variations of the vasodilator effects of sodium nitropr usside and glyceryl trinitrate on isolated smooth muscle have been stu died on rings of rat thoracic aorta, both endothelium-intact and endot helium-denuded. For most of the concentrations of sodium nitroprusside used the induced relaxations were significantly dependent on the time the tissues were obtained. However, significant temporal differences were obtained for glyceryl trinitrate-induced relaxations at lower con centrations only for both endothelium-intact and endothelium-denuded p reparations. EC50 values of sodium nitroprusside and glyceryl trinitra te (i.e. the concentrations inducing half the maximum response) were a lso significantly different and they had quite similar rhythmic featur es both in endothelium-intact and in endothelium-denuded preparations. These results clearly show that the in-vitro sensitivity of rat thora cic aorta to nitrodilator agents varies over a 24-h period and thus de pends on when the animals were killed; the presence of endothelium doe s not change the rhythm of nitrodilator activity. These variations mig ht be a result of circadian rhythm in the guanylate cyclase-cGMP syste m which mediates responses to nitrodilator agents.