Contributions of prostacyclin and nitric oxide to carbon monoxide-induced cerebrovascular dilation in piglets

Charles Leffler, Alberto Nasjletti, Robert A. Johnson, Alexander L. Fedinec

Research output: Contribution to journalArticle

48 Citations (Scopus)

Abstract

Carbon monoxide (CO) is an endogenous dilator in the newborn cerebral microcirculation. Other dilators include prostanoids and nitric oxide (NO), and interactions among the systems are likely. Experiments on anesthetized piglets with cranial windows address the hypothesis that CO-induced dilation of pial arterioles involves interaction with the prostanoid and NO systems. Topical application of CO or the heme oxygenase substrate heme-L-lysinate (HLL) produced dilation. Indomethacin, Nω-nitro-L-arginine (L-NNA), and either iberiotoxin or tetraethylammonium chloride (TEA) were used to inhibit prostanoids, NO, and Ca2+-activated K+ (KCa) channels, respectively. Indomethacin, L-NNA, iberiotoxin, or TEA blocked cerebral vasodilation to CO and HLL. Vasodilations to both CO and HLL were returned to indomethacin-treated piglets by topical application of iloprost. Vasodilations to both CO and HLL were returned to L-NNA-treated piglets by sodium nitroprusside but not iloprost. In iberiotoxin- or TEA-treated piglets, dilations to CO and HLL could not be restored by either iloprost or sodium nitroprusside. The dilator actions of CO involve prostacyclin and NO as permissive enablers. The permissive actions of prostacyclin and NO may alter the KCa channel response to CO because neither iloprost nor sodium nitroprusside could restore dilation to CO when these channels were blocked.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume280
Issue number4 49-4
StatePublished - Apr 1 2001

Fingerprint

Epoprostenol
Carbon Monoxide
Dilatation
Nitric Oxide
Iloprost
Tetraethylammonium
Nitroprusside
Vasodilation
Indomethacin
Prostaglandins
Calcium-Activated Potassium Channels
Heme Oxygenase (Decyclizing)
Arterioles
Microcirculation
Arginine
heme lysinate

All Science Journal Classification (ASJC) codes

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Cite this

Contributions of prostacyclin and nitric oxide to carbon monoxide-induced cerebrovascular dilation in piglets. / Leffler, Charles; Nasjletti, Alberto; Johnson, Robert A.; Fedinec, Alexander L.

In: American Journal of Physiology - Heart and Circulatory Physiology, Vol. 280, No. 4 49-4, 01.04.2001.

Research output: Contribution to journalArticle

@article{04315ebc742d42edbe349dc936b29284,
title = "Contributions of prostacyclin and nitric oxide to carbon monoxide-induced cerebrovascular dilation in piglets",
abstract = "Carbon monoxide (CO) is an endogenous dilator in the newborn cerebral microcirculation. Other dilators include prostanoids and nitric oxide (NO), and interactions among the systems are likely. Experiments on anesthetized piglets with cranial windows address the hypothesis that CO-induced dilation of pial arterioles involves interaction with the prostanoid and NO systems. Topical application of CO or the heme oxygenase substrate heme-L-lysinate (HLL) produced dilation. Indomethacin, Nω-nitro-L-arginine (L-NNA), and either iberiotoxin or tetraethylammonium chloride (TEA) were used to inhibit prostanoids, NO, and Ca2+-activated K+ (KCa) channels, respectively. Indomethacin, L-NNA, iberiotoxin, or TEA blocked cerebral vasodilation to CO and HLL. Vasodilations to both CO and HLL were returned to indomethacin-treated piglets by topical application of iloprost. Vasodilations to both CO and HLL were returned to L-NNA-treated piglets by sodium nitroprusside but not iloprost. In iberiotoxin- or TEA-treated piglets, dilations to CO and HLL could not be restored by either iloprost or sodium nitroprusside. The dilator actions of CO involve prostacyclin and NO as permissive enablers. The permissive actions of prostacyclin and NO may alter the KCa channel response to CO because neither iloprost nor sodium nitroprusside could restore dilation to CO when these channels were blocked.",
author = "Charles Leffler and Alberto Nasjletti and Johnson, {Robert A.} and Fedinec, {Alexander L.}",
year = "2001",
month = "4",
day = "1",
language = "English (US)",
volume = "280",
journal = "American Journal of Physiology",
issn = "0363-6135",
publisher = "American Physiological Society",
number = "4 49-4",

}

TY - JOUR

T1 - Contributions of prostacyclin and nitric oxide to carbon monoxide-induced cerebrovascular dilation in piglets

AU - Leffler, Charles

AU - Nasjletti, Alberto

AU - Johnson, Robert A.

AU - Fedinec, Alexander L.

PY - 2001/4/1

Y1 - 2001/4/1

N2 - Carbon monoxide (CO) is an endogenous dilator in the newborn cerebral microcirculation. Other dilators include prostanoids and nitric oxide (NO), and interactions among the systems are likely. Experiments on anesthetized piglets with cranial windows address the hypothesis that CO-induced dilation of pial arterioles involves interaction with the prostanoid and NO systems. Topical application of CO or the heme oxygenase substrate heme-L-lysinate (HLL) produced dilation. Indomethacin, Nω-nitro-L-arginine (L-NNA), and either iberiotoxin or tetraethylammonium chloride (TEA) were used to inhibit prostanoids, NO, and Ca2+-activated K+ (KCa) channels, respectively. Indomethacin, L-NNA, iberiotoxin, or TEA blocked cerebral vasodilation to CO and HLL. Vasodilations to both CO and HLL were returned to indomethacin-treated piglets by topical application of iloprost. Vasodilations to both CO and HLL were returned to L-NNA-treated piglets by sodium nitroprusside but not iloprost. In iberiotoxin- or TEA-treated piglets, dilations to CO and HLL could not be restored by either iloprost or sodium nitroprusside. The dilator actions of CO involve prostacyclin and NO as permissive enablers. The permissive actions of prostacyclin and NO may alter the KCa channel response to CO because neither iloprost nor sodium nitroprusside could restore dilation to CO when these channels were blocked.

AB - Carbon monoxide (CO) is an endogenous dilator in the newborn cerebral microcirculation. Other dilators include prostanoids and nitric oxide (NO), and interactions among the systems are likely. Experiments on anesthetized piglets with cranial windows address the hypothesis that CO-induced dilation of pial arterioles involves interaction with the prostanoid and NO systems. Topical application of CO or the heme oxygenase substrate heme-L-lysinate (HLL) produced dilation. Indomethacin, Nω-nitro-L-arginine (L-NNA), and either iberiotoxin or tetraethylammonium chloride (TEA) were used to inhibit prostanoids, NO, and Ca2+-activated K+ (KCa) channels, respectively. Indomethacin, L-NNA, iberiotoxin, or TEA blocked cerebral vasodilation to CO and HLL. Vasodilations to both CO and HLL were returned to indomethacin-treated piglets by topical application of iloprost. Vasodilations to both CO and HLL were returned to L-NNA-treated piglets by sodium nitroprusside but not iloprost. In iberiotoxin- or TEA-treated piglets, dilations to CO and HLL could not be restored by either iloprost or sodium nitroprusside. The dilator actions of CO involve prostacyclin and NO as permissive enablers. The permissive actions of prostacyclin and NO may alter the KCa channel response to CO because neither iloprost nor sodium nitroprusside could restore dilation to CO when these channels were blocked.

UR - http://www.scopus.com/inward/record.url?scp=0035007161&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0035007161&partnerID=8YFLogxK

M3 - Article

C2 - 11247758

AN - SCOPUS:0035007161

VL - 280

JO - American Journal of Physiology

JF - American Journal of Physiology

SN - 0363-6135

IS - 4 49-4

ER -