Ischemia reduces CGRP-induced cerebral vascular dilation in piglets.

Abstract:

BACKGROUND AND PURPOSE:Effects of anoxic stress on cerebrovascular responses to calcitonin gene-related peptide (CGRP) have not been examined previously. We determined the effects of total global ischemia on cerebral arteriolar responses to CGRP in newborn pigs. METHODS:Piglets were anesthetized and ventilated with a respirator. Pial arteriolar diameter was determined using a closed cranial window and intravital microscopy. Baseline arteriolar diameters ranged from 80 to 100 microns. Arteriolar responses to 10(-9) and 10(-8) mmol/L CGRP applied topically were determined before and 1, 2, and 4 hours after a 10-minute period of total global ischemia. Ischemia was caused by increasing intracranial pressure. RESULTS:Before ischemia, CGRP dilated arterioles by 14 +/- 2% (n = 6) and 24 +/- 3% (n = 7) at 10(-9) and 10(-8) mmol/L, respectively. However, after ischemia, arteriolar responses to 10(-9) mmol/L CGRP were reduced at 1 hour to 4 +/- 1%, at 2 hours to 3 +/- 2%, and at 4 hours to 5 +/- 4% (P < .05 for all comparisons). Similarly, arteriolar responses to 10(-8) mmol/L CGRP were reduced to 5 +/- 2% at 1 hour, 5 +/- 2% at 2 hours, and 10 +/- 6% at 4 hours (P < .05 for all comparisons). In time control animals, arteriolar responses to CGRP did not change over time. In other animals, we examined effects of pretreatment with indomethacin (5 mg/kg IV) on ischemia-induced decreases in arteriolar responses to CGRP. Indomethacin administration did not preserve arteriolar dilation to CGRP at 1 hour after ischemia, but responses were normal at 2 hours. CONCLUSIONS:Total global ischemia leads to prolonged attenuated dilator responses of cerebral arterioles to CGRP. In addition, indomethacin treatment alters effects of ischemia on CGRP-induced dilation.

journal_name

Stroke

journal_title

Stroke

authors

Louis TM,Meng W,Bari F,Errico RA,Busija DW

doi

10.1161/01.str.27.1.134

subject

Has Abstract

pub_date

1996-01-01 00:00:00

pages

134-8; discussion 139

issue

1

eissn

0039-2499

issn

1524-4628

journal_volume

27

pub_type

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