Nitric oxide modulates epicardial coronary basal vasomotor tone in awake dogs

Chu, Alan; Chambers, David; Lin, Chang-Chyi; Kuehl, W. D.; Cobb, Frederick R.

doi:10.1152/ajpheart.1990.258.4.h1250

Cited by 56 publications

(39 citation statements)

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“…Our results are compatible with some animal studies that have examined the role of NO on basal coronary vascular tone (14,15,20) but differ from other studies ( 18,21,40 (20). A study using L-NMMA in human coronary arteries (32) demonstrated inhibition of ACH-induced dilation of distal epicardial coronary arteries only, but no effect was observed in either the proximal epicardial vessels or the coronary microvessels.…”

Section: Comparison With Previous Studiessupporting

confidence: 87%

“…One important endotheliumderived relaxing factor has been characterized as nitric oxide (NO), or a compound closely related to NO (10)(11)(12). The capacity of blood vessels to release NO at rest or with stimulation is variable between organs and species (13)(14)(15)(16)(17)(18)(19)(20)(21)(22). Studies of human coronary endothelial function have largely relied on stimulating production of endothelium-derived relaxing factor with ACH (8,9,(23)(24)(25)(26)(27)(28)(29)(30)(31).…”

Section: Introductionmentioning

confidence: 99%

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Nitric oxide activity in the human coronary circulation. Impact of risk factors for coronary atherosclerosis.

Quyyumi¹,

Dakak²,

Andrews³

et al. 1995

J. Clin. Invest.

422

203

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The bioavailability of nitric oxide (NO) in the human coronary circulation at rest and after acetylcholine (ACH)-induced vasodilation was investigated in 32 patients with angiographically normal coronary arteries. The effects of intracoronary L-NG monomethyl arginine (L-NMMA) were investigated at rest and after ACH, sodium nitroprusside, and adenosine. L-NMMA (64 ,mol/min) increased resting coronary vascular resistance by 22% (P < 0.001), reduced distal epicardial coronary artery diameter by 12.6% (P < 0.001), and inhibited ACH-induced coronary epicardial and microvascular vasodilation. These effects were reversed with intracoronary L-arginine. L-NMMA did not inhibit dilation in response to sodium nitroprusside and adenosine.23 patients were exposed to one or more coronary risk factors. The vasoconstrictor effect of L-NMMA on the epicardial and microvessels was greater in patients free of risk factors: Coronary vascular resistance was 36% higher in patients without risks, compared to 17% higher in patients with risks (P < 0.05). Both epicardial and microvascular dilator effects of ACH were greater in patients without risk factors, and the inhibition of these effects by L-NMMA was also greater in patients without risk factors.Thus: (a) NO contributes importantly to resting epicardial and coronary microvascular tone, (b) coronary vascular dilation in response to ACH is predominantly due to increased production of NO, and (c) despite the absence of angiographic evidence of atherosclerosis, exposure to coronary risk factors is associated with reduced resting and stimulated bioavailability of NO from the human coronary circulation. (J. Clin. Invest. 1995. 95:1747-1755

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Section: Comparison With Previous Studiessupporting

confidence: 87%

Section: Introductionmentioning

confidence: 99%

Nitric oxide activity in the human coronary circulation. Impact of risk factors for coronary atherosclerosis.

Quyyumi¹,

Dakak²,

Andrews³

et al. 1995

J. Clin. Invest.

422

203

View full text Add to dashboard Cite

show abstract

“…5,11 Conversely, competitive inhibition of NO synthesis with monomethyl-L-arginine caused a decrease in coronary artery diameter but did not decrease coronary blood flow. 12 These findings support the concept that in the normal heart, NO contributes to tonic vasodilation of coronary arteries. Using intravital microscopy, Jones et al 13 observed that inhibition of endogenous NO production with N-nitro-Larginine methyl ester caused constriction of small coronary resistance arteries (100 to 400 m) in open-chest dogs, but this was offset by vasodilation of the arterioles (Ͻ100 m) and resulted in no significant change in blood flow.…”

Section: Effect Of Pde5 Inhibition On Normal Coronary Circulationsupporting

confidence: 75%

Cyclic Nucleotide Phosphodiesterase Type 5 Activity Limits Blood Flow to Hypoperfused Myocardium During Exercise

Traverse

Chen

et al. 2000

Circulation

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Background-Nitric oxide (NO) causes vasodilation by stimulation of guanylate cyclase in vascular smooth muscle to produce cGMP. The resultant vasodilator effect is regulated by a family of cGMP phosphodiesterases (PDEs). Sildenafil, a selective inhibitor of PDE5 used for treatment of erectile dysfunction, has been found to cause relaxation of isolated epicardial coronary artery segments. The present study examined the effects of sildenafil on coronary blood flow and hemodynamics during exercise in normal and ischemic heart. Methods and Results-In chronically instrumented normal dogs, sildenafil 2 mg/kg PO caused a slight but significant increase in left anterior descending (LAD) coronary blood flow during resting conditions, with a nonsignificant trend toward increased coronary flow during treadmill exercise. Exercise in the presence of LAD stenosis that decreased distal coronary pressure to 57Ϯ2 mm Hg reduced LAD flow during exercise from 69Ϯ8 to 41Ϯ7 mL/min (PϽ0.05), with hypoperfusion most severe in the subendocardium. At the same distal coronary pressure, sildenafil increased LAD flow in the ischemic region to 50Ϯ11 mL/min (PϽ0.05). Increase in ischemic region blood flow produced by sildenafil was uniform across the LV wall, given that no change occurred in the transmural distribution of perfusion. Conclusions-Inhibition of PDE5 with sildenafil caused vasodilation of coronary resistance vessels with an increase of blood flow into an ischemic myocardial region during exercise in the presence of coronary artery stenosis. (Circulation.

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“…The changes in basal coronary vasomotion and stimulated endothelium-dependent responses were reversed by a high dose ofL-arginine. In an earlier study, in a different group of animals, we described the effects of a low dose of L-NMMA, 5 mg/kg on basal coronary vasomotion (23). The present study extends this initial observation to a wide range ofinhibition ofNO production and assess effects on stimulated as well as basal vasomotion for the first time.…”

Section: Discussionsupporting

confidence: 54%

Effects of inhibition of nitric oxide formation on basal vasomotion and endothelium-dependent responses of the coronary arteries in awake dogs.

Chu

Chambers²,

Lin³

et al. 1991

J. Clin. Invest.

190

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The role of nitric oxide in basal vasomotor tone and stimulated endothelium-dependent dilations in the coronary arteries in chronically instrumented awake dogs was studied by examining the consequences of inhibiting endogenous nitric oxide formation with the specific inhibitor of nitric oxide formation, NGmonomethyl-L-arginine (L-NMMA). In four awake dogs, coronary dimension crystals were chronically implanted on the circumflex artery for the measurement of epicardial coronary diameter, and Doppler flow probes were implanted for quantitation of phasic coronary blood flow (vasomotion of distal regulatory resistance vessels). Basal epicardial coronary diameter, acetylcholine-stimulated endothelium-dependent dilation, and flow-induced endothelium-dependent dilation of the epicardial arteries and phasic blood flow were recorded before, and after 5, 15, 50, and 120 mg/kg of L-NMMA. L-NMMA induced a dose-related increase in basal epicardial coronary vasomotor tone. There was an accompanying increase in aortic pressure and a decrease in heart rate. At doses 2 50 mg/kg, rest phasic coronary blood flow was also decreased. Left ventricular enddiastolic pressure and contractility were not significantly changed. In contrast, the flow-induced or acetylcholine-stimulated endothelium-dependent responses were attenuated only after infusion of the highest doses of L-NMMA (120 mg/kg). The changes in the basal vasomotor tone and acetylcholinestimulated endothelium-dependent responses returned towards the control states in the presence of L-arginine (660 mg/kg). These data support the view that nitric oxide plays a significant role in modulating basal vasomotion and endothelial-dependent dilation stimulated by acetylcholine or increase in blood flow in epicardial coronary arteries and also influence the regulation of coronary blood flow during physiologic conditions. (J. Clin.

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Nitric oxide modulates epicardial coronary basal vasomotor tone in awake dogs

Cited by 56 publications

References 0 publications

Nitric oxide activity in the human coronary circulation. Impact of risk factors for coronary atherosclerosis.

Nitric oxide activity in the human coronary circulation. Impact of risk factors for coronary atherosclerosis.

Cyclic Nucleotide Phosphodiesterase Type 5 Activity Limits Blood Flow to Hypoperfused Myocardium During Exercise

Effects of inhibition of nitric oxide formation on basal vasomotion and endothelium-dependent responses of the coronary arteries in awake dogs.

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