title: Influence of endothelium on the vasoconstrictor effect of dihydroergotamine in pithed rats.
abstract: 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.
authors.affiliation: Institute of Pharmacology and Toxicology, Medical Academy Erfurt, Germany.
authors.forename: H
authors.initials: H
authors.lastname: Müller
authors.forename: E
authors.initials: E
authors.lastname: Glusa
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D003655:Decerebrate State / Q000503:physiopathology; D004087:Dihydroergotamine / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000502:physiology*; D008297:Male; D009569:Nitric Oxide / Q000502:physiology; D009638:Norepinephrine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013223:Statistics as Topic; D014661:Vasoconstriction / Q000187:drug effects* / Q000502:physiology
chemical_list: D009569:Nitric Oxide; D004087:Dihydroergotamine; D009638:Norepinephrine