Influence of vascular tone on vasoconstrictor responses to the 5-HT 1-like receptor agonist sumatriptan in anaesthetised rabbits.
The cardiovascular profile of the 5-HT1-like receptor agonist sumatriptan has been studied in anaesthetised rabbits pretreated with chlorisondamine (0.5 mg kg-1 i.v.) and enalapril (0.3 mg kg-1 i.v.) to eliminate autonomic reflexes and minimise endogenous vasoconstrictor tone. Under these conditions sumatriptan (2-100 micrograms kg-1 i.v.) produced modest increases in carotid vascular resistance but had no significant influence on heart rate, blood pressure or mesenteric vascular resistance. In a similarly pretreated group of animals in which vasoconstrictor tone was elevated by infusion of angiotensin (100 ng kg-1 min-1 i.v.) sumatriptan caused moderate increases in blood pressure (55 +/- 5 to 65 +/- 5 mm Hg after 25 micrograms kg-1 i.v.) and mesenteric vascular resistance (1.4 +/- 0.2 to 1.6 +/- 0.2 mm Hg min ml-1 after 25 micrograms kg-1 i.v.) and tended to produce a greater carotid vasoconstriction (3.6 +/- 0.5 to 4.7 +/- 0.7 mm Hg min ml-1 after 25 micrograms kg-1). These effects were antagonised by methiothepin 0.3 mg kg-1 i.v. implying the involvement of 5-HT1-like receptor stimulation. Hence, the presence of angiotensin produces a modest amplification of the vasoconstrictor effects of sumatriptan and, in particular, unmasks a constriction of the mesenteric vascular bed. The degree of synergy observed between these two vasoconstrictors was, however, less marked than might have been expected on the basis of previous isolated tissue studies.
Choppin
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Synthélabo Recherche, Department of Preclinical Research, Bagneux, France.
O'Connor
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D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D002714:Chlorisondamine / Q000494:pharmacology; D004357:Drug Synergism; D004656:Enalapril / Q000494:pharmacology; D005730:Ganglionic Blockers / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D008719:Methiothepin / Q000494:pharmacology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology*; D011817:Rabbits; D012039:Regional Blood Flow / Q000187:drug effects; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D018170:Sumatriptan / Q000494:pharmacology*; D014655:Vascular Resistance / Q000187:drug effects; D014661:Vasoconstriction; D014662:Vasoconstrictor Agents / Q000494:pharmacology
D000959:Antihypertensive Agents; D005730:Ganglionic Blockers; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D014662:Vasoconstrictor Agents; D000804:Angiotensin II; D008719:Methiothepin; D004656:Enalapril; D018170:Sumatriptan; D002714:Chlorisondamine