Kainate-induced cerebrovascular dilation is resistant to ischemia in piglets.

Abstract

BACKGROUND AND PURPOSE:

Cerebral arteriolar dilation to N-methyl-D-aspartate (NMDA) is drastically reduced by anoxic stress. The effects of anoxic stress on cerebrovascular dilation to activation of other types of glutamate receptors are unknown. The purpose of this study was to examine the effects of ischemia on cerebral arteriolar responses to kainate in anesthetized piglets.

METHODS:

Arteriolar responses to 5 x 10(-5) mol/L and 10(-4) mol/L kainate were evaluated before and 10 minutes after total, global ischemia. Ischemia was induced by increasing intracranial pressure. We measured pial arteriolar diameters (approximately 100 microns) using a cranial window and intravital microscopy.

RESULTS:

Before ischemia, kainate dilated arterioles by 16 +/- 2% at 5 x 10% mol/L and 30 +/- 2% at 10(-4) mol/L (mean +/- SEM; n = 6). After ischemia, the diameter of arterioles increased by 17 +/- 3% and 26 +/- 3% to 5 x 10% and 10(-4) mol/L kainate, respectively (P > .05). We also investigated the mechanisms involved in mediating arteriolar dilation to kainate. Intravenous administration of N omega-nitro-L-arginine methyl ester (L-NAME) (15 mg/kg) (n = 7) or indomethacin (10 mg/kg) (n = 6) individually reduced arteriolar dilation to kainate by approximately one half. Coadministration of L-NAME and indomethacin almost completely eliminated arteriolar dilation to kainate (n = 10). Administration of theophylline (20 mg/kg IV) did not affect dilator responses to kainate (n = 7). Blockade of NMDA receptors by MK801 had minimal effects on arteriolar dilation to kainate (n = 6).

CONCLUSIONS:

There are three main findings from this study: (1) kainate is a potent dilator agent in the neonatal cerebral circulation; (2) nitric oxide and prostaglandins both participate in the vasodilator response to kainate; and (3) in contrast to NMDA, cerebral arteriolar dilator responses to kainate are resistant to ischemic stress.

• Authors: F Bari, T M Louis, D W Busija
• Journal: Stroke (Stroke) Vol. 28 Issue 6 Pg. 1272-6; discussion 1277 (Jun 1997) ISSN: 0039-2499 [Print] United States
• PMID: 9183361 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Excitatory Amino Acid Antagonists
• Prostaglandins
• Vasodilator Agents
• Nitric Oxide
• Dizocilpine Maleate
• Theophylline
• Kainic Acid
• NG-Nitroarginine Methyl Ester
• Indomethacin

Topics

• Animals
• Animals, Newborn
• Arterioles (drug effects, physiopathology)
• Brain Ischemia (physiopathology)
• Cerebral Arteries (drug effects, physiopathology)
• Dizocilpine Maleate (pharmacology)
• Excitatory Amino Acid Antagonists (pharmacology)
• Female
• Indomethacin (pharmacology)
• Kainic Acid (antagonists & inhibitors, pharmacology)
• Male
• NG-Nitroarginine Methyl Ester (pharmacology)
• Nitric Oxide (physiology)
• Prostaglandins (physiology)
• Reperfusion Injury (physiopathology)
• Swine
• Theophylline (pharmacology)
• Vasodilator Agents (pharmacology)