The effect of NG‐nitro‐L‐arginine methyl ester upon hindlimb blood flow responses to muscle contraction in the anaesthetized cat

Poucher, SM

doi:10.1113/expphysiol.1995.sp003843

Cited by 12 publications

(7 citation statements)

References 14 publications

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“…Nevertheless, in all experiments, L-NAME reduced the increase in FVC and FBF during the recovery period. These findings are consistent with those of many previous studies on rats (Hirai et al 1994), cats (Poucher, 1995), dogs (Shen et al 2000) and humans (e.g. Dyke et al 1995;Shoemaker et al 1997;Frandsen et al 2001).…”

Section: Contribution Of Nitric Oxide To Exercise-induced Vasodilatatsupporting

confidence: 93%

“…It was these findings that led us to propose that the generation of adenosine in systemic hypoxia depends on a background level of NO being present to bind to endothelial cytochrome c oxidase, increasing its sensitivity to falls in P O 2 and facilitating adenosine release (Edmunds et al 2003). By contrast, in the present study, although infusion of SNAP in the presence of NOS inhibition restored the increase in FVC evoked by muscle contraction as reported in the cat (Poucher, 1995), the component of the 'restored' dilatation that was attributable to adenosine acting via A 2A -receptors was certainly no greater than in the presence of NOS inhibition alone. Thus, we can propose, contrary to our working hypotheses (see introduction), that the generation of adenosine during muscle contraction is unlikely to be dependent on a tonic level of NO binding to cytochrome c oxidase of skeletal muscle or endothelial mitochondria and sensitizing the respiratory chain to a local fall in P O 2 .…”

Section: Contribution Of Nitric Oxide To Exercise-induced Vasodilatatsupporting

confidence: 52%

“…Indeed, L-NAME reduced baseline hindlimb blood flow by 45% in anaesthetized cats and attenuated the hyperaemia evoked by twitch contractions. However, when the baseline blood flow was restored with the NO donor sodium nitroprusside (SNP), the hyperaemia during muscle contraction was fully restored (Poucher, 1995). These results suggested that synthesis of NO is not necessary for the vasodilatation that accompanied muscle contraction, but that it is NO dependent.…”

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confidence: 99%

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Nitric oxide (NO) does not contribute to the generation or action of adenosine during exercise hyperaemia in rat hindlimb

Ray

Marshall

2009

The Journal of Physiology

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Exercise hyperaemia is partly mediated by adenosine A 2A -receptors. Adenosine can evoke nitric oxide (NO) release via endothelial A 2A -receptors, but the role for NO in exercise hyperaemia is controversial. We have investigated the contribution of NO to hyperaemia evoked by isometric twitch contractions in its own right and in interaction with adenosine. In three groups of anaesthetized rats the effect of A 2A -receptor inhibition with ZM241385 on femoral vascular conductance (FVC) and hindlimb O 2 consumption (V O 2 ) at rest and during isometric twitch contractions (4 Hz) was tested (i) after NO synthase inhibition with l-NAME, and when FVC had been restored by infusion of (ii) an NO donor (SNAP) or (iii) cell-permeant cGMP. Exercise hyperaemia was significantly reduced (32%) by l-NAME and further significantly attenuated by ZM241385 (60% from control). After restoring FVC with SNAP or 8-bromo-cGMP, l-NAME did not affect exercise hyperaemia, but ZM241385 still significantly reduced the hyperaemia by 25%. There was no evidence that NO limited muscleV O 2 during contraction. These results indicate that NO is not required for adenosine release during contraction and that adenosine released during contraction does not depend on new synthesis of NO to produce vasodilatation. They also substantiate our general hypothesis that the mechanisms by which adenosine contributes to muscle vasodilatation during systemic hypoxia and exercise are different: we propose that, during muscle contraction, adenosine is released from skeletal muscle fibres independently of NO and acts directly on A 2A -receptors on the vascular smooth muscle to cause vasodilatation.

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Section: Contribution Of Nitric Oxide To Exercise-induced Vasodilatatsupporting

confidence: 93%

Section: Contribution Of Nitric Oxide To Exercise-induced Vasodilatatsupporting

confidence: 52%

mentioning

confidence: 99%

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Nitric oxide (NO) does not contribute to the generation or action of adenosine during exercise hyperaemia in rat hindlimb

Ray

Marshall

2009

The Journal of Physiology

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“…These include flow‐related shear stress, acetylcholine, insulin, and insulin‐like growth factor I. NO also plays a major role in reactive hyperaemia of limb muscle (Poucher 1995). The role of NO in exercise hypaeremia is more controversial.…”

Section: No Effects On Vascular Controlmentioning

confidence: 99%

Role of nitric oxide in skeletal muscle: synthesis, distribution and functional importance

Reid

1998

Acta Physiologica Scandinavica

222

195

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Over the last two decades, nitric oxide (NO) has been established as a novel mediator of biological processes, ranging from vascular control to long-term memory, from tissue inflammation to penile erection. This paper reviews recent research which shows that NO and its derivatives also are synthesized within skeletal muscle and that NO derivatives influence various aspects of muscle function. Individual muscle fibres express one or both of the constitutive NO synthase (NOS) isoforms. Type I (neuronal) NOS is localized to the sarcolemma of fast fibres; type III (endothelial) NOS is associated with mitochondria. Isolated skeletal muscle produces NO at low rates under resting conditions and at higher rates during repetitive contraction. NO appears to mediate cell-cell interactions in muscle, including vasodilation and inhibition of leucocyte adhesion. NO also acts directly on muscle fibres to alter cell function. Muscle metabolism appears to be NO-sensitive at several sites, including glucose uptake, glycolysis, mitochondrial oxygen consumption and creatine kinase activity. NO also modulates muscle contraction, inhibiting force output by altering excitation-contraction coupling. The mechanisms of NO action are likely to include direct effects on redox-sensitive regulatory proteins, interaction with endogenous reactive oxygen species, and activation of second messengers such as cyclic guanosine monophosphate (cGMP). In conclusion, research published over the past few years makes it clear that skeletal muscle produces NO and that endogenous NO modulates muscle function. Much remains to be learned, however, about the physiological importance of NO actions and about their underlying mechanisms.

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“…In these small arteries increases in diameter at constant pressure cause an increase in flow and the net effect of an increase in flow is, in contrast to the situation in large‐conduit arteries, an increase in shear stress. However, the diameter of small arteries is determined much more by the physical and metabolic environment of the surrounding tissue making it difficult to detect the precise role of flow‐mediated dilatation in vivo (Poucher, 1995).…”

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confidence: 99%

Characteristics of the response of the iliac artery to wall shear stress in the anaesthetized pig

Kelly

Snow

2007

The Journal of Physiology

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The functional significance of shear stress-induced vasodilatation in large conduit arteries is unclear since changes in the diameter have little effect on the resistance to blood flow. However, changes in diameter have a relatively large effect on wall shear stress which suggests that the function of flow-mediated dilatation is to reduce wall shear stress. The mean and pulsatile components of shear stress vary widely throughout the arterial system and areas of low mean and high amplitude of wall shear stress are prone to the development of atheroma. In this study, using an in vivo model with the ability to control flow rate and amplitude of flow independently, we investigated the characteristics of the response of the iliac artery to variations in both the mean and amplitude of wall shear stress. The results of this study confirm that increases in mean wall shear stress are an important stimulus for the release of nitric oxide by the endothelium as indicated by changes in arterial diameter and show for the first time, in vivo, that increases in the amplitude of the pulsatile component of shear stress have a small but significant inhibitory effect on this response. A negative feedback mechanism was identified whereby increases in shear stress brought about by increases in blood flow are reduced by the release of nitric oxide from the endothelium causing dilatation of the artery, thus decreasing the stimulus to cell adhesion and, through a direct action of nitric oxide, inhibiting the process of cell adhesion. The results also provide an explanation for the uneven distribution of atheroma throughout the arterial system, which is related to the ratio of pulsatile to mean shear stress and consequent variability in the production of NO. Flow-mediated dilatation of large conduit arteries was first demonstrated in vivo by Schretzenmayr (1933) and was later shown to be caused by the action of an increase in wall shear stress on the endothelium (Melkumyants et al. 1989) which causes vasodilatation by production of nitric oxide (NO) (Griffith et al. 1984). The functional significance of this dilatation is unclear since changes in the diameter of conduit arteries (e. g. aorta, iliac and femoral) have little effect on the resistance to blood flow, which is determined by the diameter of small-resistance arteries, in particular the arterioles. However, changes in diameter do have a relatively large effect on wall shear stress, which is inversely proportional to the diameter cubed at constant flow and viscosity, thus suggesting the existence of a negative feedback system whereby increases in wall shear stress, brought about, for example, by increases in flow, are reduced by dilatation of the conduit artery. Flow-mediated dilatation has also been directly observed in isolated small-resistance arteries (Sorop et al. 2003) and by implication from perfusion experiments in vivo (Kartamyshev et al. 2007). In these small arteries increases in diameter at constant pressure cause an increase in flow and the net effect of an increase i...

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The effect of NG‐nitro‐L‐arginine methyl ester upon hindlimb blood flow responses to muscle contraction in the anaesthetized cat

Cited by 12 publications

References 14 publications

Nitric oxide (NO) does not contribute to the generation or action of adenosine during exercise hyperaemia in rat hindlimb

Nitric oxide (NO) does not contribute to the generation or action of adenosine during exercise hyperaemia in rat hindlimb

Role of nitric oxide in skeletal muscle: synthesis, distribution and functional importance

Characteristics of the response of the iliac artery to wall shear stress in the anaesthetized pig

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