The permissive role of endothelial NO in CO-induced cerebrovascular dilation

Ebrahim Barkoudah, Jonathan Jaggar, Charles Leffler

Research output: Contribution to journalArticle

44 Citations (Scopus)

Abstract

Carbon monoxide (CO) and nitric oxide (NO) are important paracrine messengers in the newborn cerebrovasculature that may act as comessengers. Here, we investigated the role of NO in CO-mediated dilations in the newborn cerebrovasculature. Arteriolar branches of the middle cerebral artery (100-200 μm) were isolated from 3- to 7-day-old piglets and cannulated at each end in a superfusion chamber, and intravascular pressure was elevated to 30 mmHg, which resulted in the development of myogenic tone. Endothelium removal abolished dilations of pressurized pial arterioles to bradykinin and to the CO-releasing molecule Mn2(CO)10 [dimanganese decacarbonyl (DMDC)] but not dilations to isoproterenol. With endothelium intact, Nω- nitro-L-arginine (L-NNA), 1H-[1,2,4]oxadiazolo-[4,3-a]quinoxalin-1-one (ODQ), or tetraethylammonium chloride (TEA+), inhibitors of NO synthase (NOS), guanylyl cyclase, and large-conductance Ca2+-activated K+ (KCa) channels, respectively, also blocked dilation induced by DMDC. After inhibition of NOS, a constant concentration of sodium nitroprusside (SNP), a NO donor that only dilated the vessel 6%, returned dilation to DMDC. The stable cGMP analog 8-bromo-cGMP also restored dilation to DMDC in endothelium-intact, L-NNA-treated, or endothelium-denuded arterioles, and this effect was blocked by TEA+. Similarly, in the continued presence of ODQ, 8-bromo-cGMP restored DMDC-induced dilations. These findings suggest that endothelium-derived NO stimulates guanylyl cyclase in vascular smooth muscle cells and, thereby, permits CO to cause dilation by activating KCa channels. Such a requirement for NO could explain the endothelium dependency of CO-induced dilation in piglet pial arterioles.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume287
Issue number4 56-4
DOIs
StatePublished - Oct 1 2004

Fingerprint

Carbon Monoxide
Dilatation
Nitric Oxide
Endothelium
Arterioles
Guanylate Cyclase
Nitric Oxide Synthase
Calcium-Activated Potassium Channels
Tetraethylammonium
Nitric Oxide Donors
Middle Cerebral Artery
Nitroprusside
Bradykinin
Vascular Smooth Muscle
Isoproterenol
Smooth Muscle Myocytes
Arginine
dimanganese decacarbonyl
Pressure

All Science Journal Classification (ASJC) codes

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

Cite this

@article{213e2be260ee46739190fafa0e3a0dee,
title = "The permissive role of endothelial NO in CO-induced cerebrovascular dilation",
abstract = "Carbon monoxide (CO) and nitric oxide (NO) are important paracrine messengers in the newborn cerebrovasculature that may act as comessengers. Here, we investigated the role of NO in CO-mediated dilations in the newborn cerebrovasculature. Arteriolar branches of the middle cerebral artery (100-200 μm) were isolated from 3- to 7-day-old piglets and cannulated at each end in a superfusion chamber, and intravascular pressure was elevated to 30 mmHg, which resulted in the development of myogenic tone. Endothelium removal abolished dilations of pressurized pial arterioles to bradykinin and to the CO-releasing molecule Mn2(CO)10 [dimanganese decacarbonyl (DMDC)] but not dilations to isoproterenol. With endothelium intact, Nω- nitro-L-arginine (L-NNA), 1H-[1,2,4]oxadiazolo-[4,3-a]quinoxalin-1-one (ODQ), or tetraethylammonium chloride (TEA+), inhibitors of NO synthase (NOS), guanylyl cyclase, and large-conductance Ca2+-activated K+ (KCa) channels, respectively, also blocked dilation induced by DMDC. After inhibition of NOS, a constant concentration of sodium nitroprusside (SNP), a NO donor that only dilated the vessel 6{\%}, returned dilation to DMDC. The stable cGMP analog 8-bromo-cGMP also restored dilation to DMDC in endothelium-intact, L-NNA-treated, or endothelium-denuded arterioles, and this effect was blocked by TEA+. Similarly, in the continued presence of ODQ, 8-bromo-cGMP restored DMDC-induced dilations. These findings suggest that endothelium-derived NO stimulates guanylyl cyclase in vascular smooth muscle cells and, thereby, permits CO to cause dilation by activating KCa channels. Such a requirement for NO could explain the endothelium dependency of CO-induced dilation in piglet pial arterioles.",
author = "Ebrahim Barkoudah and Jonathan Jaggar and Charles Leffler",
year = "2004",
month = "10",
day = "1",
doi = "10.1152/ajpheart.00369.2004",
language = "English (US)",
volume = "287",
journal = "American Journal of Physiology",
issn = "0363-6135",
publisher = "American Physiological Society",
number = "4 56-4",

}

TY - JOUR

T1 - The permissive role of endothelial NO in CO-induced cerebrovascular dilation

AU - Barkoudah, Ebrahim

AU - Jaggar, Jonathan

AU - Leffler, Charles

PY - 2004/10/1

Y1 - 2004/10/1

N2 - Carbon monoxide (CO) and nitric oxide (NO) are important paracrine messengers in the newborn cerebrovasculature that may act as comessengers. Here, we investigated the role of NO in CO-mediated dilations in the newborn cerebrovasculature. Arteriolar branches of the middle cerebral artery (100-200 μm) were isolated from 3- to 7-day-old piglets and cannulated at each end in a superfusion chamber, and intravascular pressure was elevated to 30 mmHg, which resulted in the development of myogenic tone. Endothelium removal abolished dilations of pressurized pial arterioles to bradykinin and to the CO-releasing molecule Mn2(CO)10 [dimanganese decacarbonyl (DMDC)] but not dilations to isoproterenol. With endothelium intact, Nω- nitro-L-arginine (L-NNA), 1H-[1,2,4]oxadiazolo-[4,3-a]quinoxalin-1-one (ODQ), or tetraethylammonium chloride (TEA+), inhibitors of NO synthase (NOS), guanylyl cyclase, and large-conductance Ca2+-activated K+ (KCa) channels, respectively, also blocked dilation induced by DMDC. After inhibition of NOS, a constant concentration of sodium nitroprusside (SNP), a NO donor that only dilated the vessel 6%, returned dilation to DMDC. The stable cGMP analog 8-bromo-cGMP also restored dilation to DMDC in endothelium-intact, L-NNA-treated, or endothelium-denuded arterioles, and this effect was blocked by TEA+. Similarly, in the continued presence of ODQ, 8-bromo-cGMP restored DMDC-induced dilations. These findings suggest that endothelium-derived NO stimulates guanylyl cyclase in vascular smooth muscle cells and, thereby, permits CO to cause dilation by activating KCa channels. Such a requirement for NO could explain the endothelium dependency of CO-induced dilation in piglet pial arterioles.

AB - Carbon monoxide (CO) and nitric oxide (NO) are important paracrine messengers in the newborn cerebrovasculature that may act as comessengers. Here, we investigated the role of NO in CO-mediated dilations in the newborn cerebrovasculature. Arteriolar branches of the middle cerebral artery (100-200 μm) were isolated from 3- to 7-day-old piglets and cannulated at each end in a superfusion chamber, and intravascular pressure was elevated to 30 mmHg, which resulted in the development of myogenic tone. Endothelium removal abolished dilations of pressurized pial arterioles to bradykinin and to the CO-releasing molecule Mn2(CO)10 [dimanganese decacarbonyl (DMDC)] but not dilations to isoproterenol. With endothelium intact, Nω- nitro-L-arginine (L-NNA), 1H-[1,2,4]oxadiazolo-[4,3-a]quinoxalin-1-one (ODQ), or tetraethylammonium chloride (TEA+), inhibitors of NO synthase (NOS), guanylyl cyclase, and large-conductance Ca2+-activated K+ (KCa) channels, respectively, also blocked dilation induced by DMDC. After inhibition of NOS, a constant concentration of sodium nitroprusside (SNP), a NO donor that only dilated the vessel 6%, returned dilation to DMDC. The stable cGMP analog 8-bromo-cGMP also restored dilation to DMDC in endothelium-intact, L-NNA-treated, or endothelium-denuded arterioles, and this effect was blocked by TEA+. Similarly, in the continued presence of ODQ, 8-bromo-cGMP restored DMDC-induced dilations. These findings suggest that endothelium-derived NO stimulates guanylyl cyclase in vascular smooth muscle cells and, thereby, permits CO to cause dilation by activating KCa channels. Such a requirement for NO could explain the endothelium dependency of CO-induced dilation in piglet pial arterioles.

UR - http://www.scopus.com/inward/record.url?scp=4744369363&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=4744369363&partnerID=8YFLogxK

U2 - 10.1152/ajpheart.00369.2004

DO - 10.1152/ajpheart.00369.2004

M3 - Article

VL - 287

JO - American Journal of Physiology

JF - American Journal of Physiology

SN - 0363-6135

IS - 4 56-4

ER -