Role of nitric oxide and carbon monoxide in Nω-Nitro-l-arginine methyl ester-resistant acetylcholine-induced relaxation in chicken carotid artery

Marie Dennis Leo, Yeshavanth K.B. Siddegowda, Dinesh Kumar, Surendra K. Tandan, Kochiganti V.H. Sastry, Vellanki Ravi Prakash, Santosh K. Mishra

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

The current study examined the hypothesis that acetylcholine-induced Nω-Nitro-l-arginine methyl ester (l-NAME)-resistant endothelium-dependent relaxations in the chicken carotid artery are mediated by nitric oxide and carbon monoxide. Acetylcholine (1 nM-3 μM) caused a concentration-dependent relaxation (pD2 6.81 ± 0.05, Rmax 115 ± 3%) of the artery segments precontracted with phenylephrine (3 μM). l-NAME (1 mM) decreased the sensitivity (pD2 6.44 ± 0.06), but not the efficacy (Rmax 108 ± 3%) of acetylcholine. It also partially decreased the acetylcholine (3 μM)-stimulated nitrite release. While treatment with Nω-Nitro-l-arginine (l-NNA; 1 mM) plus l-NAME (1 mM) decreased the acetylcholine-stimulated nitrite release to the basal level, it moderately inhibited (Rmax 77 ± 3%) the maximal relaxation elicited with the muscarinic agonist. 2-Phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl 3-oxide (PTIO; 100 μM) a specific scavenger of nitric oxide (NO) plus the two NOS inhibitors further decreased the acetylcholine-evoked relaxation (Rmax 34 ± 2%). Although soluble guanylyl cyclase (sGC) inhibitor 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ; 10 μM) markedly inhibited the acetylcholine-stimulated increase in tissue cGMP to less than the basal levels, it only decreased the sensitivity, but not the efficacy of the agonist either in the presence or absence of l-NAME (1 mM). Zinc Protoporphyrin-IX (ZnPP; 10 μM), a hemeoxygenase (HO) inhibitor, partially inhibited (Rmax 72 ± 3%) the l-NAME-resistant acetylcholine-induced relaxations. A combined treatment of the arterial rings with l-NAME, l-NNA, PTIO and ZnPP nearly abolished (Rmax 7 ± 0.9%) the vasodilator responses to acetylcholine. Endothelium removal abolished the relaxation response to acetylcholine. In conclusion, it is suggested that the acetylcholine-induced l-NAME-resistant relaxation is primarily, mediated by NO with a small but significant contribution from endothelium-derived carbon monoxide in the chicken carotid artery.

Original languageEnglish (US)
Pages (from-to)111-117
Number of pages7
JournalEuropean Journal of Pharmacology
Volume596
Issue number1-3
DOIs
StatePublished - Oct 31 2008
Externally publishedYes

Fingerprint

Carbon Monoxide
Carotid Arteries
Acetylcholine
Chickens
Nitric Oxide
Endothelium
Nitrites
arginine methyl ester
Muscarinic Agonists
Phenylephrine
Vasodilator Agents
Arginine
Arteries

All Science Journal Classification (ASJC) codes

  • Pharmacology

Cite this

Role of nitric oxide and carbon monoxide in Nω-Nitro-l-arginine methyl ester-resistant acetylcholine-induced relaxation in chicken carotid artery. / Leo, Marie Dennis; Siddegowda, Yeshavanth K.B.; Kumar, Dinesh; Tandan, Surendra K.; Sastry, Kochiganti V.H.; Prakash, Vellanki Ravi; Mishra, Santosh K.

In: European Journal of Pharmacology, Vol. 596, No. 1-3, 31.10.2008, p. 111-117.

Research output: Contribution to journalArticle

Leo, Marie Dennis ; Siddegowda, Yeshavanth K.B. ; Kumar, Dinesh ; Tandan, Surendra K. ; Sastry, Kochiganti V.H. ; Prakash, Vellanki Ravi ; Mishra, Santosh K. / Role of nitric oxide and carbon monoxide in Nω-Nitro-l-arginine methyl ester-resistant acetylcholine-induced relaxation in chicken carotid artery. In: European Journal of Pharmacology. 2008 ; Vol. 596, No. 1-3. pp. 111-117.
@article{fa7799a7226348ecb75b3efd96ab13bd,
title = "Role of nitric oxide and carbon monoxide in Nω-Nitro-l-arginine methyl ester-resistant acetylcholine-induced relaxation in chicken carotid artery",
abstract = "The current study examined the hypothesis that acetylcholine-induced Nω-Nitro-l-arginine methyl ester (l-NAME)-resistant endothelium-dependent relaxations in the chicken carotid artery are mediated by nitric oxide and carbon monoxide. Acetylcholine (1 nM-3 μM) caused a concentration-dependent relaxation (pD2 6.81 ± 0.05, Rmax 115 ± 3{\%}) of the artery segments precontracted with phenylephrine (3 μM). l-NAME (1 mM) decreased the sensitivity (pD2 6.44 ± 0.06), but not the efficacy (Rmax 108 ± 3{\%}) of acetylcholine. It also partially decreased the acetylcholine (3 μM)-stimulated nitrite release. While treatment with Nω-Nitro-l-arginine (l-NNA; 1 mM) plus l-NAME (1 mM) decreased the acetylcholine-stimulated nitrite release to the basal level, it moderately inhibited (Rmax 77 ± 3{\%}) the maximal relaxation elicited with the muscarinic agonist. 2-Phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl 3-oxide (PTIO; 100 μM) a specific scavenger of nitric oxide (NO) plus the two NOS inhibitors further decreased the acetylcholine-evoked relaxation (Rmax 34 ± 2{\%}). Although soluble guanylyl cyclase (sGC) inhibitor 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ; 10 μM) markedly inhibited the acetylcholine-stimulated increase in tissue cGMP to less than the basal levels, it only decreased the sensitivity, but not the efficacy of the agonist either in the presence or absence of l-NAME (1 mM). Zinc Protoporphyrin-IX (ZnPP; 10 μM), a hemeoxygenase (HO) inhibitor, partially inhibited (Rmax 72 ± 3{\%}) the l-NAME-resistant acetylcholine-induced relaxations. A combined treatment of the arterial rings with l-NAME, l-NNA, PTIO and ZnPP nearly abolished (Rmax 7 ± 0.9{\%}) the vasodilator responses to acetylcholine. Endothelium removal abolished the relaxation response to acetylcholine. In conclusion, it is suggested that the acetylcholine-induced l-NAME-resistant relaxation is primarily, mediated by NO with a small but significant contribution from endothelium-derived carbon monoxide in the chicken carotid artery.",
author = "Leo, {Marie Dennis} and Siddegowda, {Yeshavanth K.B.} and Dinesh Kumar and Tandan, {Surendra K.} and Sastry, {Kochiganti V.H.} and Prakash, {Vellanki Ravi} and Mishra, {Santosh K.}",
year = "2008",
month = "10",
day = "31",
doi = "10.1016/j.ejphar.2008.07.058",
language = "English (US)",
volume = "596",
pages = "111--117",
journal = "European Journal of Pharmacology",
issn = "0014-2999",
publisher = "Elsevier",
number = "1-3",

}

TY - JOUR

T1 - Role of nitric oxide and carbon monoxide in Nω-Nitro-l-arginine methyl ester-resistant acetylcholine-induced relaxation in chicken carotid artery

AU - Leo, Marie Dennis

AU - Siddegowda, Yeshavanth K.B.

AU - Kumar, Dinesh

AU - Tandan, Surendra K.

AU - Sastry, Kochiganti V.H.

AU - Prakash, Vellanki Ravi

AU - Mishra, Santosh K.

PY - 2008/10/31

Y1 - 2008/10/31

N2 - The current study examined the hypothesis that acetylcholine-induced Nω-Nitro-l-arginine methyl ester (l-NAME)-resistant endothelium-dependent relaxations in the chicken carotid artery are mediated by nitric oxide and carbon monoxide. Acetylcholine (1 nM-3 μM) caused a concentration-dependent relaxation (pD2 6.81 ± 0.05, Rmax 115 ± 3%) of the artery segments precontracted with phenylephrine (3 μM). l-NAME (1 mM) decreased the sensitivity (pD2 6.44 ± 0.06), but not the efficacy (Rmax 108 ± 3%) of acetylcholine. It also partially decreased the acetylcholine (3 μM)-stimulated nitrite release. While treatment with Nω-Nitro-l-arginine (l-NNA; 1 mM) plus l-NAME (1 mM) decreased the acetylcholine-stimulated nitrite release to the basal level, it moderately inhibited (Rmax 77 ± 3%) the maximal relaxation elicited with the muscarinic agonist. 2-Phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl 3-oxide (PTIO; 100 μM) a specific scavenger of nitric oxide (NO) plus the two NOS inhibitors further decreased the acetylcholine-evoked relaxation (Rmax 34 ± 2%). Although soluble guanylyl cyclase (sGC) inhibitor 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ; 10 μM) markedly inhibited the acetylcholine-stimulated increase in tissue cGMP to less than the basal levels, it only decreased the sensitivity, but not the efficacy of the agonist either in the presence or absence of l-NAME (1 mM). Zinc Protoporphyrin-IX (ZnPP; 10 μM), a hemeoxygenase (HO) inhibitor, partially inhibited (Rmax 72 ± 3%) the l-NAME-resistant acetylcholine-induced relaxations. A combined treatment of the arterial rings with l-NAME, l-NNA, PTIO and ZnPP nearly abolished (Rmax 7 ± 0.9%) the vasodilator responses to acetylcholine. Endothelium removal abolished the relaxation response to acetylcholine. In conclusion, it is suggested that the acetylcholine-induced l-NAME-resistant relaxation is primarily, mediated by NO with a small but significant contribution from endothelium-derived carbon monoxide in the chicken carotid artery.

AB - The current study examined the hypothesis that acetylcholine-induced Nω-Nitro-l-arginine methyl ester (l-NAME)-resistant endothelium-dependent relaxations in the chicken carotid artery are mediated by nitric oxide and carbon monoxide. Acetylcholine (1 nM-3 μM) caused a concentration-dependent relaxation (pD2 6.81 ± 0.05, Rmax 115 ± 3%) of the artery segments precontracted with phenylephrine (3 μM). l-NAME (1 mM) decreased the sensitivity (pD2 6.44 ± 0.06), but not the efficacy (Rmax 108 ± 3%) of acetylcholine. It also partially decreased the acetylcholine (3 μM)-stimulated nitrite release. While treatment with Nω-Nitro-l-arginine (l-NNA; 1 mM) plus l-NAME (1 mM) decreased the acetylcholine-stimulated nitrite release to the basal level, it moderately inhibited (Rmax 77 ± 3%) the maximal relaxation elicited with the muscarinic agonist. 2-Phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl 3-oxide (PTIO; 100 μM) a specific scavenger of nitric oxide (NO) plus the two NOS inhibitors further decreased the acetylcholine-evoked relaxation (Rmax 34 ± 2%). Although soluble guanylyl cyclase (sGC) inhibitor 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ; 10 μM) markedly inhibited the acetylcholine-stimulated increase in tissue cGMP to less than the basal levels, it only decreased the sensitivity, but not the efficacy of the agonist either in the presence or absence of l-NAME (1 mM). Zinc Protoporphyrin-IX (ZnPP; 10 μM), a hemeoxygenase (HO) inhibitor, partially inhibited (Rmax 72 ± 3%) the l-NAME-resistant acetylcholine-induced relaxations. A combined treatment of the arterial rings with l-NAME, l-NNA, PTIO and ZnPP nearly abolished (Rmax 7 ± 0.9%) the vasodilator responses to acetylcholine. Endothelium removal abolished the relaxation response to acetylcholine. In conclusion, it is suggested that the acetylcholine-induced l-NAME-resistant relaxation is primarily, mediated by NO with a small but significant contribution from endothelium-derived carbon monoxide in the chicken carotid artery.

UR - http://www.scopus.com/inward/record.url?scp=53049094896&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=53049094896&partnerID=8YFLogxK

U2 - 10.1016/j.ejphar.2008.07.058

DO - 10.1016/j.ejphar.2008.07.058

M3 - Article

VL - 596

SP - 111

EP - 117

JO - European Journal of Pharmacology

JF - European Journal of Pharmacology

SN - 0014-2999

IS - 1-3

ER -