Differential effects of verapamil and flunarizine on epinephrine-induced vasoconstriction and on spontaneous vasomotion of arterioles in skeletal muscle in the rat in vivo.
The effects of verapamil and of flunarizine on the epinephrine-induced vasoconstriction and on the spontaneous vasomotion of third-to-fourth-order arterioles (range 9-25 microns diameter) in the rat cremaster muscle were compared, using quantitative intravital microscopy. Verapamil as well as flunarizine [0.5 mg/kg intravenously (i.v.) in 10 s; 10-50 min postmedication] similarly reduced the submaximal arteriolar vasoconstriction induced by topically applied epinephrine (maximal concentrations 1 x 10(-7) and 1 x 10(-6) M), illustrating their inhibitory action against stimulated Ca2+ influx into vascular smooth muscle cells at the doses examined. Verapamil increased the basal arteriolar diameter (+54.6%), and reduced the frequency (-82.1%) and velocity (-65.8%) of the spontaneously cyclic changes in the diameter of arterioles, typical for the autoregulation of microcirculatory blood flow. In contrast, flunarizine slightly increased basal arteriolar diameter (+16.5%) but did not modify the pattern of spontaneous arteriolar vasomotion. The effect of verapamil and inactivity of flunarizine on the spontaneous arteriolar vasomotion may result from an interference by the former drug with the myogenic activity of vascular smooth muscle cells, caused by Ca2+ translocations in physiologic conditions and the lack of such an interference by the latter compound. These observations performed on the same blood vessels corroborate the differentiation between Ca2+ slow channel blockers (verapamil) and Ca2+ overload blockers (flunarizine) in vivo.
De Clerck
F
F
Department of Haematology, Janssen Research Foundation, Beerse, Belgium.
Loots
W
W
Voeten
J
J
Janssen
P A
PA
D000818:Animals; D001160:Arterioles / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D002118:Calcium / Q000502:physiology; D004837:Epinephrine / Q000494:pharmacology*; D005444:Flunarizine / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009132:Muscles / Q000098:blood supply*; D051381:Rats; D011919:Rats, Inbred Strains; D012039:Regional Blood Flow / Q000187:drug effects; D013997:Time Factors; D014661:Vasoconstriction / Q000187:drug effects*; D014700:Verapamil / Q000494:pharmacology*
D014700:Verapamil; D005444:Flunarizine; D002118:Calcium; D004837:Epinephrine