Enhancement of vasoconstrictor and attenuation of vasodilator effects of 5-hydroxytryptamine by the calcium channel blockers nimodipine and nifedipine in the pig.

As calcium (Ca2+) channel blockers are effective against the vasoconstrictor responses to 5-hydroxytryptamine (5-HT) in vitro, and a favourable response is claimed for these drugs in migraine prophylaxis, we studied the interaction between nimodipine or nifedipine, and 5-HT for effects on carotid haemodynamics in the anaesthetized pig. Intracarotid infusions of nimodipine (0.25 microgram X kg-1 X min-1), nifedipine (0.75 microgram X kg-1 X min-1) or 5-HT (2.0 micrograms X kg-1 X min-1) caused a redistribution of carotid blood flow in favour of the nutrient (capillary) fraction at the expense of the non-nutrient (arteriovenous anastomoses; AVA) fraction. Compared to those of 5-HT, the effects of the Ca2+ channel blockers on cranial AVAs were much weaker and the increase in the capillary fraction was observed mainly in the skeletal muscles, rather than in the skin and ears as with 5-HT. When 5-HT was infused in the presence of nimodipine or nifedipine, the amine-induced vasoconstrictor responses in the total carotid vascular bed and its AVA fraction were either not attenuated or were increased while the vasodilator responses were reduced. We conclude that: in contrast to what was found in vitro, the 5-HT-induced vasoconstriction in vivo, involving either '5-HT1-like' (AVAs) or 5-HT2 (arterioles) receptors, was not antagonized by nimodipine or nifedipine; the attenuation of the 5-HT-induced dermal vasodilatation by the two Ca2+ channel blockers is most likely to be the result of a 'steal' due to the profound vasodilatation in the skeletal muscle region; and the comparatively mild reduction in AVA conductance caused by the Ca2+ channel blockers may be one of the reasons for their inability to abort acute attacks of migraine. The increase in nutrient blood flow is of potential benefit, but whether this property of the Ca2+ channel blockers is linked to their usefulness in migraine prophylaxis remains to be ascertained.