L-arginine infusion promotes nitric oxide-dependent vasodilation, increases regional cerebral blood flow, and reduces infarction volume in the rat.

Morikawa, Eiharu; Moskowitz, Michael A.; Huang, Zhihong; Yoshida, Tomoo; Irikura, Katsumi; Dalkara, Turgay

doi:10.1161/01.str.25.2.429

Cited by 219 publications

(138 citation statements)

References 29 publications

(16 reference statements)

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“…Several lines of evidence suggest that the improvement of CBF is causally linked to the improved tissue outcome. First, it is well established that interventions that improve CBF in the ischemic territory, such as NO donors, ameliorate the tissue damage (Morikawa et al, 1994;. It is therefore likely that the CBF improvement produced by LPS administration has similar beneficial consequences.…”

Section: Discussionmentioning

confidence: 99%

Neurovascular Protection by Ischemic Tolerance: Role of Nitric Oxide and Reactive Oxygen Species

Kunz¹,

Park²,

Abe³

et al. 2007

J. Neurosci.

131

117

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Cerebral ischemic preconditioning or tolerance is a powerful neuroprotective phenomenon by which a sublethal injurious stimulus renders the brain resistant to a subsequent damaging ischemic insult. We used lipopolysaccharide (LPS) as a preconditioning stimulus in a mouse model of middle cerebral artery occlusion (MCAO) to examine whether improvements in cerebrovascular function contribute to the protective effect. Administration of LPS 24 h before MCAO reduced the infarct by 68% and improved ischemic cerebral blood flow (CBF) by 114% in brain areas spared from infarction. In addition, LPS prevented the dysfunction in cerebrovascular regulation induced by MCAO, as demonstrated by normalization of the increase in CBF produced by neural activity, hypercapnia, or by the endotheliumdependent vasodilator acetylcholine. These beneficial effects of LPS were not observed in mice lacking inducible nitric oxide synthase (iNOS) or the nox2 subunit of the superoxide-producing enzyme NADPH oxidase. LPS increased reactive oxygen species and the peroxynitrite marker 3-nitrotyrosine in wild-type mice but not in nox2 nulls. The peroxynitrite decomposition catalyst 5,10,15, 20-tetrakis(4-sulfonatophenyl)porphyrinato iron (III) attenuated LPS-induced nitration and counteracted the beneficial effects of LPS on infarct volume, ischemic CBF, and vascular reactivity. Thus, LPS preserves neurovascular function and ameliorates CBF in regions of the ischemic territory at risk for infarction. This effect is mediated by peroxynitrite formed from iNOS-derived NO and nox2-derived superoxide. The data indicate that preservation of cerebrovascular function is an essential component of ischemic tolerance and suggest that combining neuroprotection and vasoprotection may be a valuable strategy for treating ischemic brain injury.

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Section: Discussionmentioning

confidence: 99%

Neurovascular Protection by Ischemic Tolerance: Role of Nitric Oxide and Reactive Oxygen Species

Kunz¹,

Park²,

Abe³

et al. 2007

J. Neurosci.

131

117

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“…However, GTN forms NO, which is a potent modulator of cerebrovascular reactivity, especially in collateral vessels, such as pial arteries. 25,26 Vascular NO levels are low in stroke, 27 so collateral vessels may not be maximally dilated. Hence, CBF might be held constant with GTN if moderate reductions in systemic BP were counterbalanced by increases in collateral blood supply, which would be potentially beneficial in acute stroke.…”

Section: Discussionmentioning

confidence: 99%

Transdermal Glyceryl Trinitrate Lowers Blood Pressure and Maintains Cerebral Blood Flow in Recent Stroke

et al. 2006

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Abstract-High blood pressure (BP) is common in acute stroke and is independently associated with a poor outcome.Lowering BP might improve outcome if it did not adversely affect cerebral blood flow (CBF) or cerebral perfusion pressure. We investigated the effect of glyceryl trinitrate ([GTN] an NO donor) on quantitative CBF, BP, and cerebral perfusion pressure in patients with recent stroke. Eighteen patients with recent (Ͻ5 days) ischemic (nϭ16) or hemorrhagic (nϭ2) stroke were randomly assigned (2:1) to transdermal GTN (5 mg) or control. CBF (global, hemispheric, arterial territory, and lesion, using xenon computed tomography) and BP (peripheral and central) were measured before and 1 hour after treatment with GTN. The effects of GTN on CBF and BP were adjusted for baseline measurements (ANCOVA

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“…Although a great deal of research has been conducted on the effects of exogenous L-arginine on the circulatory system, most of the studies have focused on the effect of L-arginine administration on blood pressure in experimental models of hypertension (20)(21)(22) and in patients (16,23,24); the improvement of blood flow or exercise capacity in patients with chronic heart failure (17), hypertension (18), and hypercholesterolemia (25); and the prevention of atherosclerosis (11). Few reports exist on the effect of L-arginine on capillary blood flow in normotensive subjects (16,(26)(27)(28)(29). The therapeutic effect of L-arginine supplementation in improving exercise capacity in healthy subjects has often been attributed to an increase in plasma growth hormone levels (27)(28)(29).…”

Section: Discussionmentioning

confidence: 99%

Low-dose l -arginine administration increases microperfusion of hindlimb muscle without affecting blood pressure in rats

Ohta

Takagi

Sato

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

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The objective of this work was to evaluate the influence of exogenous L-arginine on the capillary blood flow of peripheral tissues of normotensive subjects. Rats were anesthetized with sodium pentobarbital, and the blood flow of femoral, dorsal, and ventral skin and gastrocnemius and soleus muscle was measured by laser Doppler flow and microsphere methods to compare the blood flow before and after the L-arginine infusion. L-Arginine lowered the mean blood pressure in a dose-dependent manner, but a statistically significant reduction in mean blood pressure was detected only at a high dose of 500 mg/kg of body weight. The significant blood flow increment was detected after the L-arginine infusion at doses of 50 and 150 mg/kg without causing hypotension. Nicardipine, a calcium channel blocker, also increased the skin blood flow, but the blood flow increment and blood pressure fall were comparable. A significant increment in microperfusion was detected in gastrocnemius, soleus muscle, and ventral skin compared with control group by the microsphere method. No adverse effects were observed during L-arginine and microsphere infusion. The present work indicates that L-arginine infusion increases muscle capillary blood flow in rats that are not performing exercise. Supplementation with L-arginine might provide additional blood flow at rest and during exercise and result in the improvement of muscle performance and exercise capacity.exercise ͉ nitric oxide N itric oxide (NO) is a widespread signaling molecule that is involved in mammalian physiological processes including the relaxation of blood vessels (1-3), immune function (4), inhibition of platelet aggregation (5, 6), and neurotransmission (7). The amino acid L-arginine is the natural precursor for the formation of NO (8), and exogenous L-arginine administration causes the relaxation of blood vessels through the action of NO (9, 10). Although NO synthase, the enzyme that produces NO from L-arginine, is theoretically saturated with its natural substrate, exogenous L-arginine administration leads to increased NO production, and this phenomenon is known as the arginine paradox (9, 10). Therefore, many investigators have been interested in the effects of supplementation with L-arginine to produce increased beneficial effects of NO, including prevention of the progression of atherosclerosis (11, 12), prevention of pulmonary artery endothelial dysfunction (13, 14), enhancement of cellular immune response of T lymphocytes (4), and amelioration of hypertension (15,16). Other studies indicate that oral supplementation of L-arginine also corrects endothelial dysfunction of chronic heart failure (17), and it increases exercise capacity in patients with precapillary pulmonary hypertension by increasing peak oxygen consumption and decreasing pulmonary arterial pressure and pulmonary vascular resistance thorough the action of NO (18).Because oxygen and carbon dioxide exchange takes place only in the capillary bed, the peripheral blood flow correlates with the rate of oxygen uptake...

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L-arginine infusion promotes nitric oxide-dependent vasodilation, increases regional cerebral blood flow, and reduces infarction volume in the rat.

Cited by 219 publications

References 29 publications

Neurovascular Protection by Ischemic Tolerance: Role of Nitric Oxide and Reactive Oxygen Species

Neurovascular Protection by Ischemic Tolerance: Role of Nitric Oxide and Reactive Oxygen Species

Transdermal Glyceryl Trinitrate Lowers Blood Pressure and Maintains Cerebral Blood Flow in Recent Stroke

Low-dose l -arginine administration increases microperfusion of hindlimb muscle without affecting blood pressure in rats

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