Vasodilatory actions of calcitonin gene-related peptide and nitric oxide in parenchymal microvessels of the rat hippocampus

Andrea Fergus, Yongcheng Jin, Quoc-Anh Thai, Neal F. Kassell, Kevin S. Lee

Research output: Contribution to journalArticle

Abstract

Calcitonin gene-related peptide (CGRP) and nitric oxide (NO) are potent dilators in a variety of vascular beds. Recent evidence suggests that NO may serve as an intermediary messenger for CGRP and/or CGRP may serve as an intermediary messenger for NO in the expression of vasodilation. The present study was designed to provide an initial characterization of the responses to NO and CGRP in parenchymal microvessels and to determine whether NO and/or CGRP act as intermediaries for one another. Microvessels in the parenchyma of in vitro hippocampal slices from rat brain were examined using computer-assisted videomicroscopy. The resting diameter of the microvessels ranged from 9 to 26 μm. Treatment with the nitric oxide synthase inhibitor, NG-nitro-l-arginine (l-NNA; 100 μM) constricted vessels to 64.2% ± 3.0% of resting luminal diameter. Sodium nitroprusside (SNP; 1 μM), a donor of NO, reversed the l-NNA-induced vasoconstriction by 77.0% ± 15.0%. CGRP alone (10 nM) elicited a small but significant vasodilatory effect on resting vascular tone (2.3% ± 0.6%). In the presence of l-NNA, CGRP elicited a significant dose-dependent vasodilatory response, and 10 nM CGRP elicited a sizeable response, reversing the l-NNA-induced constriction by 84.3% ± 15.5%. This CGRP-induced dilation was inhibited by pretreatment with the CGRP receptor antagonist, CGRP fragment (8-37) (1 μM). In contrast, pretreatment with 1 μM CGRP fragment (8-37) did not attenuate the SNP-induced dilation in the presence of l-NNA. Taken together, these findings demonstrate that CGRP and NO are potent dilators of parenchymal microvessels, and that NO provides a substantial relaxant effect on resting tone. In addition, the results indicate that CGRP is not a necessary intermediary in NO-induced dilation, and that NO is not a necessary intermediary in CGRP-induced dilation in parenchymal microvessels.

Original languageEnglish (US)
Pages (from-to)78-84
Number of pages7
JournalBrain Research
Volume694
Issue number1-2
DOIs
Publication statusPublished - Oct 2 1995
Externally publishedYes

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Keywords

  • Calcitonin gene-related peptide
  • Hippocampus
  • Microvessel
  • Nitric oxide
  • Nitric oxide synthase
  • Vasodilation

ASJC Scopus subject areas

  • Developmental Biology
  • Molecular Biology
  • Clinical Neurology
  • Neuroscience(all)

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