Influence of endothelium on the vasoconstrictor effect of dihydroergotamine in pithed rats
Müller, H.; Glusa, E.
Archives Internationales de Pharmacodynamie et de Therapie 313: 120-128
1991
ISSN/ISBN: 0003-9780 PMID: 1816759 Document Number: 386123
The aim of the present paper was to investigate whether endothelial damage influences the vasoconstrictor activity of dihydroergotamine in pithed normotensive rats. Intravenous administration of dihydroergotamine caused a dose-dependent increase in mean arterial blood pressure. Endothelial lesions were produced by a bolus injection of homocysteine (100 mg/kg) or methionine (100 mg/kg every 24 hr for 6 days). In these animals, the resting blood pressure was not influenced, while the dihydroergotamine-induced pressor effect was significantly enhanced with an increase in the maximum effect. Pretreatment of the animals with NG-nitro-L-arginine (10 mg/kg), which inhibits the biosynthesis of the endothelium-derived relaxing factor in endothelial cells, markedly enhanced the pressor response to dihydroergotamine accompanied with an increase in the maximum response. Intravenous administration of NG-nitro-L-arginine alone led to a sustained increase in blood pressure by 19 .+-. 4 mm Hg. In comparative studies with noradrenaline, the dose-response curve for the pressor effect was shifted to the left after pretreatment of the rats with methionine or NG-nitro-L-arginine, whereas the maximum effect remained unchanged. The results suggest that the impaired basal release of the endothelium-derived relaxing factor accounts for the increased vasoconstrictor activity of dihydroergotamine. This might be an explanation for the vasospastic effects of dihydroergotamine in arterial vessels with endothelial damage.