In experiments on anaesthetised rats, the roles played by adenosine and nitric oxide (NO) were determined in resting skeletal muscle in acute systemic hypoxia and during acclimation to chronic systemic hypoxia. It is concluded that adenosine acting on A1 receptors, at least in part in an NO-dependent manner, plays essential roles in causing the dilation of proximal and terminal arterioles that helps to maintain muscle O2 consumption when O2 delivery is reduced by acute systemic hypoxia. It is proposed that adenosine and NO are similarly responsible for causing the tonic vasodilation that gradually wanes in the first 7 days of chronic hypoxia and that concomitantly, adenosine and hypoxia stimulate VEGF expression, so increasing venular permeability and triggering angiogenesis. By 7 days of chronic hypoxia, arteriolar remodelling is well established and within 18-21 days, substantial capillary angiogenesis alleviates tissue hypoxia. At this time, vasoconstrictor responses to the sympathetic transmitter norepinephrine are reduced, but dilator responses to adenosine released by acute hypoxia are enhanced, as may be explained by increased sensitivity to NO. Thus, preservation of tissue oxygenation is apparently associated with impaired ability to regulate arterial pressure and vulnerability to further hypoxia.
|Number of pages||15|
|Journal||Advances in Experimental Medicine and Biology|
|Publication status||Published - 1 Jan 2002|