Chronic Inhibition of Nitric Oxide Production Augments Skin Vasoconstriction in the Rabbit Ear

Khan, Faisel; Palacino, James; Coffman, Jay D.; Cohen, Richard A.

doi:10.1097/00005344-199308000-00017

Cited by 16 publications

(11 citation statements)

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“…In animals, NO has been shown to be involved in the basal control of skin blood flow by maintaining vasodilator tone that counteracts vasoconstrictor activity. 10.1 1 In humans, however, the role of NO in regulating cutaneous vascular tone is controversial. NO has been shown to contribute to the basal dilator tone in the dorsal finger and forearm skin,'.12 which is in contrast to the findings of Noon et al!'…”

Section: Resultsmentioning

confidence: 99%

Cutaneous Vascular Responses to Acetylcholine are Mediated by a Prostanoid-Dependent Mechanism in Man

et al. 1997

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Approximately 50% of the forearm vasodilatation to intra-arterial infusions of acetylcholine is mediated by endothelium-derived nitric oxide. These conclusions have been derived from venous occlusion plethysmographic measurements of total forearm blood flow during coinfusions of acetylcholine and fIIG-monomethyl-L-arginine (L-NMMAl. an inhibitor of nitric oxide synthase. Since venous occlusion plethysmography measures total limb blood flow, the relative proportion of the measurement from skin cannot be determined precisely. To determine the effects of acetylcholine on skin specifically, we have used laser Doppler flowmetry to measure vascular responses to local iontophoresis of acetylcholine in the forearm of normal male volunteers. To elucidate the possible mechanisms of cutaneous vasodilatation to acetylcholine, vascular responses were measured before and after systemic inhibition of prostanoid production and nitric oxide synthesis by oral aspirin (600 mg daily for 3 days) and intravenous L-NMMA (3 mg/kg for 60 min), respectively. After aspirin administration, dose-dependent vascular responses to acetylcholine were reduced significantly by approximately 53% (p<0.005, ANOVA). In contrast, intravenous L-NMMA appeared to have no significant effect on cutaneous vascular responses to acetylcholine. While the role of nitric oxide is uncertain, vasodilatation to acetylcholine in the forearm skin is mediated largely by a prostanoid-dependent mechanism. Assessment of cutaneous vascular responses to iontophoresis of acetylcholine may, therefore, be useful in diseases where abnormal endothelium-dependent prostanoid function has been implicated.

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Section: Resultsmentioning

confidence: 99%

Cutaneous Vascular Responses to Acetylcholine are Mediated by a Prostanoid-Dependent Mechanism in Man

et al. 1997

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“…Chronic inhibition of NO production by L-NAME reduced the resting blood flow in the rabbit ear skin (Khan et al, 1993). Infusion of L-NMMA via a brachial artery catheter decreased forearm skin blood flow in normal subjects (Coffman, 1994).…”

Section: A Cutaneous Small Arterymentioning

confidence: 95%

The Pharmacology of Nitric Oxide in the Peripheral Nervous System of Blood Vessels

2003

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“…10 Briefly, four rings of aorta were incubated in test tubes containing physiological buffer warmed to 37°C and bubbled with 95% O 2 /5% CO 2 for 90 minutes with buffer changes every 30 minutes. After the first 50 minutes of incubation, one pair of rings was treated with L-arginine (10~3 mol/L).…”

Section: Cyclic Gmp Assaymentioning

confidence: 99%

“…Osmotic pumps (Alzet model 2ML4) were loaded with a sterile filtered solution of L-NAME (Sigma Chemical Co) that had been dissolved in deionized water and made up to a concentration based on the initial weight of each rabbit and the factory-determined mean pumping rate of 2.60±0.1 /nL/h to deliver 12 mg/kg per day. 10 The pumps were surgically implanted under sterile conditions in the scapular region. After the rabbits were anesthetized with xylazine (5 mg/kg IM) and ketamine (35 mg/kg IM), the area was shaved, and an incision (approximately 2 cm) was made laterally, exposing a subcutaneous pouch into which the pump was implanted with the flow moderator pointing away from the incision.…”

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Chronic inhibition of nitric oxide production accelerates neointima formation and impairs endothelial function in hypercholesterolemic rabbits.

Cayatte

Palacino

Horten

et al. 1994

Arterioscler Thromb

430

220

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To determine if endogenous local levels of nitric oxide (NO) modulate atherogenesis, we studied the effect of inhibiting NO with A fO -nitro-L-arginine methyl ester (L-NAME) on early neointima formation in cholesterol-fed rabbits. Male rabbits were fed for 5 weeks with a 0.5% cholesterol diet alone or treated in addition during the last 4 weeks with L-NAME (12 mg/kg per day SC) via osmotic minipump. Endothelial cell function was assessed in isolated aortic rings by vascular reactivity and levels of cyclic GMP. In L-NAME-treated rabbits there was inhibition of endotheliumdependent relaxations to acetylcholine and the calcium ionophore A23187 as well as impaired cyclic GMP accumulation in response to acetylcholine. Neointima formation in the ascending thoracic aorta was assessed by determining media and intima cross-sectional areas with computerized image analysis. N itric oxide (NO), a potent physiological vasodilator that accounts for the biological activities of endothelium-derived relaxing factor, 1 is synthesized in endothelial cells from the terminal guanidino nitrogen of L-arginine by the constitutive calciumcalmodulin-NADPH-dependent enzyme NO synthase (NOS). 2 In humans and animals with hypercholesterolemia-induced atherosclerosis, endothelium-dependent vasodilation is impaired, 35 suggesting reduced NO synthesis or action. NO has antiproliferative actions on vascular cells, 6 -7 supporting the hypothesis that the endothelial cell dysfunction observed in hypercholesterolemia could contribute to the initiation and progression of the atherosclerotic neointima. When administered in the diet of cholesterol-fed rabbits, the NO precursor L-arginine limits development of aortic atherosclerosis and improves endothelial cell function. 8 - 9 We recently reported 10 a technique for the chronic administration to rabbits of the NOS inhibitor iV G -nitro-L-arginine methyl ester ( L -N A M E ) and demonstrated its persistent systemic effects on endothelial cells and Received November 22, 1993; revision accepted February 11, 1994.From the Robert Dawson Evans Department of Clinical Research, Vascular Biology Unit, Boston University School of Medicine, Boston, Mass.Presented in part at the 66th Scientific Sessions of the American Heart Association, Atlanta, Ga, November 6-11, 1993, and published in abstract form in Circulation. 1993;88(pt 2):I-366.Correspondence to Antonio J. Cayatte, MD, Vascular Biology Unit, E-401, Department of Medicine, Boston University School of Medicine, Boston, MA 02118.Compared with rabbits that consumed the cholesterol diet alone, L-NAME-treated rabbits had significant increases in lesion area (0.29+0.04 versus 0.15±0.03 mm 2 ) and in lesion/ media ratio (0.06±0.01 versus 0.03±0.01). Plasma levels of cholesterol and fluorescent lipid peroxide products were unchanged, suggesting no difference in cholesterol metabolism or oxidation. Because arterial blood pressure was not altered by L-NAME treatment, the increased atherogenesis could not be attributed to an increase in blood pressure. mi...

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Chronic Inhibition of Nitric Oxide Production Augments Skin Vasoconstriction in the Rabbit Ear

Cited by 16 publications

References 0 publications

Cutaneous Vascular Responses to Acetylcholine are Mediated by a Prostanoid-Dependent Mechanism in Man

Cutaneous Vascular Responses to Acetylcholine are Mediated by a Prostanoid-Dependent Mechanism in Man

The Pharmacology of Nitric Oxide in the Peripheral Nervous System of Blood Vessels

Chronic inhibition of nitric oxide production accelerates neointima formation and impairs endothelial function in hypercholesterolemic rabbits.

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