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

Cardiovascular and Metabolism Department, ZENECA Pharmaceuticals, Mereside, Macclesfield, Cheshire, UK.
Experimental Physiology (Impact Factor: 2.67). 04/1995; 80(2):237-47. DOI: 10.1113/expphysiol.1995.sp003843
Source: PubMed


The aim of the present experiment was to investigate the relative contribution of nitric oxide produced in endothelial cells to functional and reactive hyperaemia in the hindlimb of anaesthetized cats. Cats (2.5-3.4 kg) were anaesthetized with alphadalone-alphalaxone, and breathed spontaneously following tracheotomy. Left hindlimb blood flow was measured with a flow probe and hyperaemia responses were monitored following 10 s occlusion of the left external iliac artery and during 20 min stimulation of the sciatic and femoral nerves at 3 Hz. This was repeated following nitric oxide synthase inhibition with NG-nitro-L-arginine methyl ester (L-NAME, 100 mg kg-1, I.V.). Following L-NAME administration, baseline hindlimb blood flow and arterial blood pressure were restored by infusion of sodium nitroprusside (range, 0.3-2.25 micrograms kg-1 min-1, I.V.). Following arterial occlusion, L-NAME reduced the peak reactive hyperaemia (6.5 +/- 0.8 vs. 4.5 +/- 1.0 ml min-1 kg-1, P < 0.05) and blood flow repayment (9.9 +/- 2.3 vs. 6.1 +/- 2.6 ml, P < 0.05) responses. In contrast, the total functional hyperaemia response during hindlimb contraction was not altered (264.7 +/- 68.2 vs. 264.4 +/- 62.8 ml kg-1, n.s.). The results of the study suggest that the production of nitric oxide from endothelial cells does not contribute to functional hyperaemia in contracting skeletal muscle, but plays a large role in reactive hyperaemia. The results imply that flow-dependent dilatation of feed arteries is mediated by NO in reactive hyperaemia.

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    • "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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    ABSTRACT: 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 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 muscle 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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    • "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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