当前位置： SCI文献检索 > JOURNAL OF NEUROSURGERY期刊下所有文献 > Characteristics of relaxation induced by calcitonin gene-related peptide in contracted rabbit basilar artery.

Characteristics of relaxation induced by calcitonin gene-related peptide in contracted rabbit basilar artery.

Abstract：

:Increasing evidence suggests that disturbances in the modulatory influence of the vasoactive peptide, calcitonin gene-related peptide (CGRP), contribute to the pathogenesis of cerebral vasospasm after subarachnoid hemorrhage (SAH). However, only limited success has been achieved in trials attempting to ameliorate vasospasm by modifying CGRP function. To better understand the potential utility of targeting CGRP-mediated relaxation, it is important both to identify the interactions CGRP may have with other elements of the vasospastic response and to characterize the mechanisms through which CGRP elicits vasodilative effects. The present studies examined the effects of CGRP on vascular responsiveness using tension measurements of ring strips of rabbit basilar artery maintained in vitro. Pretreatment of vessels with CGRP (100 nM) inhibited vasoconstrictor responses to the potent protein kinase C (PKC) activator, phorbol 12,13-dibutyrate (PDB). This particular contractile response was selected because PKC-mediated vasoconstriction is a critical component of the vasospastic response after SAH. In a posttreatment paradigm, CGRP was also found to reverse established constriction responses to PDB (2 nM) and histamine (3 microM) in a dose-dependent manner. When tested against the maximum effective dose of PDB (30 nM) in the posttreatment paradigm, CGRP (100 nM) did not elicit significant relaxation. However, after washing both of these drugs out of the test chamber, a persistent effect of CGRP was revealed: the decay of PDB-induced contraction was accelerated in vessels that had previously been treated with CGRP. These findings indicate that CGRP elicits both immediate and sustained influences on contractile responses mediated by PKC. Finally, two potential mechanisms for the vascular response to CGRP were examined. Adenosine triphosphate (ATP)-sensitive K+ channels do not appear to participate in CGRP-mediated dilation; inhibitors of these channels, glibenclamide and tolbutamide, did not block CGRP-induced relaxation. In contrast, a possible role for the nucleotide cyclic adenosine monophosphate (cAMP) in the vascular response to CGRP was indicated by the dose-dependent elevation of cAMP levels by CGRP. Together these studies indicate that CGRP can modulate the contractile response to PKC activation. These effects are associated with increases in the levels of cAMP, but occur independently of fluxes through ATP-sensitive K+ channels.

journal_name

J Neurosurg

journal_title

Journal of neurosurgery

authors

Sutter B,Suzuki S,Kassell NF,Lee KS

doi

10.3171/jns.1995.82.1.0091

subject

Has Abstract

pub_date

1995-01-01 00:00:00

pages

91-6

issue

eissn

0022-3085

issn

1933-0693

journal_volume

pub_type

杂志文章

在线工具

Characteristics of relaxation induced by calcitonin gene-related peptide in contracted rabbit basilar artery.