The effect of hemoglobin on vasodilatory effect of calcium antagonists in the isolated rabbit basilar artery.
The effect of hemoglobin on the vasodilatory effect of calcium antagonists was studied in isolated rabbit basilar arteries using an isometric tension measurement method. The ability of nimodipine to relax or inhibit contractions elicited by high K+ depolarization or serotonin (5-hydroxytryptamine, 5-HT) was investigated in control arterial rings and rings pretreated by hemoglobin. Hemoglobin (10(-6) and 10(-5) M) reduced the relaxation induced by nimodipine (10(-10) to 10(-8) M) in the rings contracted by 40 mM KCl. This reduction in relaxation was also observed with 3 x 10(-10) to 3 x 10(-9) M nicardipine, 3 x 10(-8) to 3 x 10(-7) M verapamil, and 10(-7) to 10(-6) M diltiazem. On the other hand, the effect of nimodipine was not influenced by endothelial removal or by pretreatment with 10(-5) M albumin or 10(-6) M prostaglandin F2 alpha. Hemoglobin restored the 10(-10) and 10(-9) M nimodipine-induced inhibition of the contraction elicited by CaCl2 (0.3 to 20 mM) in a K(+)-rich, Ca(++)-free solution. This restoration was greater at higher concentrations of CaCl2. Hemoglobin enhanced both the nimodipine-sensitive tonic phase and the less sensitive phasic phase of contractions produced by 10(-6) M of 5-HT. It abolished the inhibitory effect of 10(-8) and 10(-7) M nimodipine on the phasic contraction. Endothelial removal also enhanced both phases of the contraction, but did not abolish the effect of nimodipine. This study showed that the vasodilatory effect of calcium antagonists, especially nimodipine, on the vasoconstriction induced by other vasoactive substances decreased in the presence of hemoglobin.
Toshima
M
M
Department of Neurological Surgery, University of Virginia Health Sciences Center, Charlottesville.
Kassell
N F
NF
Sasaki
T
T
Tanaka
Y
Y
Machi
T
T
D000418:Albumins / Q000502:physiology; D000818:Animals; D001488:Basilar Artery / Q000187:drug effects* / Q000502:physiology; D015237:Dinoprost / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000502:physiology; D006454:Hemoglobins / Q000502:physiology*; D066298:In Vitro Techniques; D016014:Linear Models; D008297:Male; D009553:Nimodipine / Q000494:pharmacology*; D011817:Rabbits; D012701:Serotonin / Q000502:physiology; D014661:Vasoconstriction / Q000187:drug effects*; D014664:Vasodilation / Q000187:drug effects*
D000418:Albumins; D006454:Hemoglobins; D012701:Serotonin; D009553:Nimodipine; D015237:Dinoprost