The effect of hemoglobin on vasodilatory effect of calcium antagonists in the isolated rabbit basilar artery

Abstract

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.

Comparative Study of Vasodilatation After Intra-arterial Nicardipine or Dantrolene Infusion in Animal Model of Cerebral Vasospasm

“…Established dosing of nicardipine, known to exert maximum physiologic effects in terms of arterial vasodilation, was applied herein. 17,18 Loading/maintenance dosing of dantrolene seemed to be in the range of 1 or 2 mg/kg. Each IA agent was separately admixed with normal saline for microcatheter infusion in a period of 10 min.…”

Treatment of Cerebral Vasospasm With Biocompatible Controlled-Release Systems for Intracranial Drug Delivery

“…It is postulated that hemoglobin, contained in the erythrocytes exposed to the adventitial side of cerebral arteries after SAH, may be the main mediator causing vasospasm (9,38,46,59,61). One possible effect that hemoglobin has on the vasospasm cascade is the disturbance of intracellular calcium equilibrium (6,38,46), resulting in smooth muscle contraction (6).…”

“…One possible effect that hemoglobin has on the vasospasm cascade is the disturbance of intracellular calcium equilibrium (6,38,46), resulting in smooth muscle contraction (6). Likewise, it has been shown that the vasodilatory effect of calcium channel antagonists is reduced in the presence of hemoglobin in the extravascular space (59). Nicardipine is a wellknown calcium channel blocker (Table 1).…”

Effect of calcium antagonists on regional cerebral blood flow in transplanted rat brain tumors

“…Calcium antagonists have been reported to relax vascular smooth muscles and to increase the rCBF in the central nervous system [1,5]. The effect of calcium antagonists on the pial vessels and arterioles has been shown in vitro using isolated arteries [6,7] and in vivo under normal and/or ischemic conditions [8,9]. Although the potential benefit of calcium antagonists in cerebrovascular disorders as diverse as stroke and subarachnoid hemorrhage has been recognized [10][11][12], the effect of calcium antagonists on the rCBF in the malignant brain tumor has yet to be studied.…”