Nitric oxide is the mediator of both endothelium-dependent relaxation and hyperpolarization of the rabbit carotid artery

The effect of hypercholesterolemia for 10 wk on endothelium-dependent relaxations to acetylcholine was studied in isolated rings of rabbit carotid artery and abdominal aorta contracted with phenylephrine or elevated potassium. In these arteries obtained from hypercholesterolemic rabbits, endothelium-dependent relaxations to acetylcholine were not significantly different from those of normal rabbits. In normal and hypercholesterolemic arteries, partial relaxation persisted in the presence of NG-nitro-L-arginine methyl ester (L-NAME), which blocked acetylcholine-induced increases in arterial guanosine 3',5'-cyclic monophosphate (cGMP). Combined treatment with L-NAME and the calcium-dependent potassium-channel inhibitor, charybdotoxin, blocked relaxations in both groups, suggesting that L-NAME-resistant relaxations are mediated by an endothelium-derived hyperpolarizing factor. Charybdotoxin alone or depolarizing potassium had no significant effect on normal carotid artery or normal and hypercholesterolemic abdominal aorta but significantly inhibited relaxations of the carotid artery from cholesterol-fed rabbits. The enhanced role of calcium-dependent potassium channels and the hyperpolarizing factor in relaxation of the hypercholesterolemic carotid artery suggested by these results was likely related to the fact that acetylcholine failed to stimulate cGMP only in that artery. These data suggest that endothelium-dependent relaxation in these rabbit arteries is mediated by nitric oxide-cGMP-dependent and -independent mechanisms. In hypercholesterolemia, the contribution of nitric oxide-cGMP in the carotid artery is reduced, but a hyperpolarizing factor and calcium-dependent potassium channels maintain normal acetylcholine-induced relaxation.

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Enhanced role of K+ channels in relaxations of hypercholesterolemic rabbit carotid artery to NO

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.1995.269.3.h805 ◽

1995 ◽

Vol 269 (3) ◽

pp. H805-H811 ◽

Cited By ~ 16

Author(s):

S. Najibi ◽

R. A. Cohen

Keyword(s):

Carotid Artery ◽

Sodium Nitroprusside ◽

Channel Blocker ◽

Isometric Tension ◽

K Channel ◽

K Channels ◽

Rabbit Carotid Artery ◽

Cyclic Monophosphate ◽

Endothelium Dependent Relaxation

Endothelium-dependent relaxations to acetylcholine remain normal in the carotid artery of hypercholesterolemic rabbits, but unlike endothelium-dependent relaxations of normal rabbits, they are inhibited by charybdotoxin, a specific blocker of Ca(2+)-dependent K+ channels. Because nitric oxide (NO) is the mediator of endothelium-dependent relaxation and can activate Ca(2+)-dependent K+ channels directly or via guanosine 3',5'-cyclic monophosphate, the present study investigated the role of Ca(2+)-dependent K+ channels in relaxations caused by NO, sodium nitroprusside, and 8-bromoguanosine 3',5'-cyclic monophosphate (8-Brc-GMP) in hypercholesterolemic rabbit carotid artery. Isometric tension was measured in rabbit carotid artery denuded of endothelium from normal and hypercholesterolemic rabbits which were fed 0.5% cholesterol for 12 wk. Under control conditions, relaxations to all agents were similar in normal and hypercholesterolemic rabbit arteries. Charybdotoxin had no significant effect on relaxations of normal arteries to NO, sodium nitroprusside, or 8-BrcGMP, but the Ca(2+)-dependent K+ channel blocker significantly inhibited the relaxations caused by each of these agents in the arteries from hypercholesterolemic rabbits. By contrast, relaxations to the calcium channel blocker nifedipine were potentiated to a similar extent by charybdotoxin in both groups. In addition, arteries from hypercholesterolemic rabbits relaxed less than normal to sodium nitroprusside when contracted with depolarizing potassium solution. These results indicate that although nitrovasodilator relaxations are normal in the hypercholesterolemic rabbit carotid artery, they are mediated differently, and to a greater extent, by Ca(2+)-dependent K+ channels. These data also suggest that K+ channel-independent mechanism(s) are impaired in hypercholesterolemia.

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146 Adenoviral-mediated gene transfer of endothelial nitric oxide synthase to the rabbit carotid artery alters vascular reactivity

Atherosclerosis ◽

10.1016/s0021-9150(97)87568-5 ◽

1997 ◽

Vol 130 ◽

pp. S38

Author(s):

I. Kullo ◽

G. Mozes ◽

R. Schwartz ◽

P. Gloviczki ◽

T. Crotty ◽

...

Keyword(s):

Nitric Oxide ◽

Nitric Oxide Synthase ◽

Gene Transfer ◽

Carotid Artery ◽

Endothelial Nitric Oxide Synthase ◽

Vascular Reactivity ◽

Rabbit Carotid Artery ◽

Oxide Synthase ◽

Endothelial Nitric Oxide

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Development of a Large Fibromuscular Intimal Thickening Does Not Impair Endothelium-Dependent Relaxation in the Rabbit Carotid Artery

Journal of Vascular Research ◽

10.1159/000158695 ◽

1987 ◽

Vol 24 (4) ◽

pp. 192-200 ◽

Cited By ~ 2

Author(s):

T.M. Cocks ◽

J.A. Manderson ◽

P.R.L. Mosse ◽

G.R. Campbell ◽

J.A. Angus

Keyword(s):

Carotid Artery ◽

Intimal Thickening ◽

Rabbit Carotid Artery ◽

Endothelium Dependent Relaxation

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Inhalation Anesthetics Inhibit the Release of Endothelium-derived Hyperpolarizing Factor in the Rabbit Carotid Artery

Anesthesiology ◽

10.1097/00000542-199509000-00017 ◽

1995 ◽

Vol 83 (3) ◽

pp. 574-582. ◽

Cited By ~ 17

Author(s):

Volker Lischke ◽

Rudi Busse ◽

Markus Hecker

Keyword(s):

Nitric Oxide ◽

Cytochrome P450 ◽

Carotid Artery ◽

Sodium Nitroprusside ◽

Liver Microsomes ◽

Inhibitory Effect ◽

Dependent Manner ◽

Inhalation Anesthetics ◽

Rabbit Carotid Artery ◽

Relaxant Response

Background Inhalation anesthetics may interfere with the synthesis or action of endothelium-derived vasoactive factors. We investigated the effects of desflurane, enflurane, halothane, isoflurane, and sevoflurane on the release of nitric oxide and endothelium-derived hyperpolarizing factor (EDHF) in the isolated endothelium-intact carotid artery of the rabbit. Methods Isolated segments of the carotid artery were suspended in Krebs-Henseleit solution (37 degrees C) and preconstricted with phenylephrine (1 microM). Relaxations caused by acetylcholine (ACh) (0.03-10 microM) or sodium nitroprusside (0.01-10 microM) were compared in the presence or absence of the nitric oxide synthase inhibitor NG-nitro-L-arginine (0.1 mM) in segments exposed to desflurane (8%), enflurane (2-4%), halothane (2-3.5%), isoflurane (2-4%), or sevoflurane (2%) as well as in NG-nitro-L- arginine-treated segments exposed to enflurane (2%) in combination with the KCa(+)-channel blocker tetrabutylammonium (0.3 mM) or the cytochrome P450 inhibitor clotrimazole (3 microM). Results Desflurane, enflurane, and sevoflurane selectively inhibited the ACh-induced release of EDHF. Halothane and isoflurane also weakly affected the nitric oxide-mediated relaxant response to ACh. The inhibitory effect of these two anesthetics on EDHF release was concentration-dependent. Relaxations induced by sodium nitroprusside were not inhibited by any of the anesthetics tested. Three structurally unrelated cytochrome P450 inhibitors clotrimazole (0.1 mM), metyrapone (1 mM), and SKF525a (proadifen, 0.1 mM) abolished the EDHF-mediated relaxation elicited by ACh. The pharmacologic profile of the inhibitory effect of enflurane on the release of EDHF closely resembled that of clotrimazole but not that of tetrabutylammonium. Moreover, all anesthetics inhibited the cytochrome P450-catalyzed O-dealkylation of 7-ethoxycoumarin by rabbit liver microsomes in a concentration-dependent manner. Conclusions Inhalation anesthetics significantly attenuate the EDHF-mediated relaxant response to ACh in the rabbit carotid artery. This effect appears to be attributable to inhibition of the cytochrome P450-dependent synthesis of EDHF by the endothelium.

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