The role of active smooth-muscle contraction in the occurrence of chronic vasospasm in the canine two-hemorrhage model.
To evaluate the pathogenetic role of alterations in the physical properties of the arterial wall (the passive component) and of active smooth-muscle contraction (the active component) in the occurrence of chronic vasospasm, the temporal profiles of these events were examined using the canine "two-hemorrhage" model. In the in vivo study, the basilar artery was exposed via the transclival approach on Day 0, 2, 4, 7, or 14. Nicardipine, followed by the protein kinase C inhibitor H-7, then papaverine were administered in a cumulative fashion, and the change in the basilar artery diameter induced by the addition of each agent was recorded angiographically. Drug administration markedly reversed the arterial narrowing caused by chronic vasospasm. When the vasodilatory effect of each agent was compared, the dilation induced by nicardipine or papaverine progressively decreased from Day 2 to Day 7, whereas that induced by H-7 increased. The in vitro experiment using arterial segments excised from the basilar artery revealed a progressive increase in arterial stiffness from Day 2 to Day 7. Also, there was a significant decrease in the initial half-circumference of the arterial segment, which was at its maximum on Days 4 and 7. However, the alteration in the initial half-circumference was considerably less than that in the angiographic diameter following subarachnoid hemorrhage. These data indicate that the augmented spontaneous tonus of the smooth muscle plays the predominant role in the occurrence of chronic vasospasm. Thus, the involvement of the protein kinase C-mediated contractile system is strongly suggested.
Matsui
T
T
Department of Neurosurgery, Saitama Medical Center/School, Japan.
Kaizu
H
H
Itoh
S
S
Asano
T
T
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D000818:Animals; D001488:Basilar Artery / Q000503:physiopathology; D004285:Dogs; D005260:Female; D002546:Ischemic Attack, Transient / Q000000981:diagnostic imaging / Q000201:enzymology / Q000503:physiopathology*; D007546:Isoquinolines / Q000494:pharmacology; D008297:Male; D008954:Models, Biological; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000503:physiopathology*; D009529:Nicardipine / Q000494:pharmacology; D010208:Papaverine / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism; D011859:Radiography; D013345:Subarachnoid Hemorrhage / Q000000981:diagnostic imaging / Q000201:enzymology / Q000503:physiopathology*; D014664:Vasodilation / Q000187:drug effects
D007546:Isoquinolines; D010879:Piperazines; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D009529:Nicardipine; D010208:Papaverine; D011493:Protein Kinase C