Impairment of endothelium-dependent vasodilation induced by acetylcholine and adenosine triphosphate following experimental subarachnoid hemorrhage.

Abstract

The effect of subarachnoid hemorrhage (SAH) on endotbelium-dependent vasodilation of isolated rabbit basilar artery was examined using an isometric tension recording method. Thirty-five rabbits that had 2 successive blood injections were divided into 3 groups: normal animals (control), 4 days, and 3 weeks after the first SAH. Acetylcholine (ACh) (10~6-10~4 M) and adenosine triphosphate (ATP) (10~6-10~4 M) were used to evoke dose-dependent vasodilation of isolated arterial rings previously contracted by 10~6 M serotonin. In the animals killed 4 days after the first SAH, both AChand ATP-induced relaxation were suppressed, and the degree of relaxation of this group was 38 ± 4.5% (mean ± SEM) and 22 ± 3.9% of the initial contractile tone in response to 10" 3 Despite extensive efforts to identify measures to dilate the narrowed arteries, no reliable measure exists for preventing vasospasm from developing or for reversing it. One of the major reasons for this inadequacy is a lack in understanding the pathogenesis of vasospasm. The cause of cerebral vasospasm following SAH is likely to be multifactorial.It has been recently suggested that impairment of the vasodilatory activity of cerebral arteries following SAH may play an important role in the pathogenesis of vasospasm. Arterial wall prostacyclin, a powerful vasodilator, decreases progressively following SAH. 8 It is well documented that endothelial damage occurs frequently after SAH. We have recently demonstrated that endothelium-dependent vasodilation induced by adenosine triphosphate (ATP) is impaired after SAH in a rabbit single hemorrhage model (T. Nakagomi, unpublished data). However, acetylcholine (ACh)-induced vasodilation was well preserved following SAH in that model. This may reflect a partial, less severe damage to the endothelium. The present experiments were conducted to investigate 1) the effect of SAH on endothelium-dependent vasodilation induced by ACh and ATP in a rabbit double hemorrhage model, which should result in more severe damage to the endothelium than a single injection model, and 2) to study the inhibitory effect of hemoglobin on endothelium-dependent vasodilation in basilar arteries exposed to SAH. Materials and Methods Animal PreparationsThirty-five male New Zealand white rabbits weighing 2.9-3.4 kg were anesthetized with an i.m. injection of ketamine (20 mg/kg), xylazine (5 mg/kg), and acepromazine (0.25 mg/kg) in a ratio of 8:1:1. The animals were intubated and received muscular paralysis with i.v. pancuronium bromide (0.08 mg/kg). Ventilation was maintained with a Harvard dual-phase control respirator. In each animal, the left ear artery was cannulated for monitoring blood pressure and withdrawing arterial blood.A 23-gauge butterfly needle was inserted into the cisterna magna percutaneously and connected to a pressure transducer via one outlet of a three-way stopcock. The other outlet was used for the injection of arterial blood. Intracranial pressure (ICP) was monitored immediately after the injection of arterial blood through the st...

Selective attenuation by perivascular blood of prostanoid-dependent cerebrovascular dilation in piglets.

“…However, in a double-injection model, responsiveness to both stimuli was reduced. 12 In addition, Kim et al 10 have reported that endothelium-dependent cerebrovascular relaxation in response to vasopressin and thrombin is reduced by the double-injection method in dogs, while other such responses to many other stimuli are preserved. Further, Svendgaard, et al 13 found that cerebrovascular dilation in response to arterial hypercapnia is attenuated in the presence of perivascular blood.…”

“…6 -7 In adult animal models of ICH, the perivascular presence of blood alters cerebrovascular responsiveness. 8 - 12 In particular, responses involving endothelium-derived relaxing factor (EDRF) and arterial hypercapnia 13 can be reduced. On the other hand, little is known concerning the effects of perivascular blood on dilator responses of the cerebral circulation in neonates.…”

Effect of subarachnoid hemorrhage on calcitonin gene-related peptide-induced relaxation in rabbit basilar artery.

“…One possible explanation is that the vascular damage produced by SAH may not be enough to promote the impairment of CGRP-induced vasodilation. Nakagomi et al 21 previously demonstrated that endothelium-dependent relaxation by acetylcholine was not impaired in the basilar artery of a rabbit sacrificed after a single injection of blood but that it was impaired in a rabbit sacrificed after two injections of blood. In spite of the possibility of conflicting results due to different models, it is likely that the presynaptic mechanism may be disturbed after SAH but that the postsynaptic mechanism may not be disturbed during the course of SAH in our model.…”

In Vitro Effects of New Generation Fungal Derived Nitric Oxide Donors on Rabbit Basilar Artery

“…One of the prongs was fixed and attached to the computer system (DI-190 portable I/O module; Dataq Instruments, Akron, Ohio, U.S.A.) for real-time recording and the other prong was moved apart slowly to stretch the artery segment. This procedure was done several times in one hour to produce a steady resting tension of 0.4 g. 17,24) The buffer was changed every 10 minutes. Then 100 ml KCl (40 mM concentration) was added to the bath to achieve KClinduced steady contraction.…”

“…Local concentrations of NO are also reduced due to the high binding affinity with oxyhemoglobin (oxyHb) derived from the subarachnoid clot around the brain surface and major blood vessels. 16,17) NO is involved in the regulation of the cerebral circulation, and is accepted as the most effective relaxing agent for the cerebral arterial network, and participates in the maintenance of resting cerebrovascular tone. 7,8) Depletion of NO is thought to be important in the pathogenesis of cerebral vasospasm.…”