Influence of endothelium on the vasoconstrictor effect of dihydroergotamine in pithed rats.
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.
Müller
H
H
Institute of Pharmacology and Toxicology, Medical Academy Erfurt, Germany.
Glusa
E
E
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
D009569:Nitric Oxide; D004087:Dihydroergotamine; D009638:Norepinephrine