Influence of vascular tone on vasoconstrictor responses to the 5-HT1-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 mu g 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 mu g kg(-1) i.v.) and mesenteric vascular resistance (1.4 +/- 0.2 to 1.6 +/- 0.2 mm Hg min ml(-1) after 25 mu g 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 mu g 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.