Role of Nitric Oxide in Exercise Sympatholysis

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Our laboratory, along with others have demonstrated a reduction in alpha adrenergic receptor responsiveness in the vasculature of exercising skeletal muscle. It has been suggested that the production of nitric oxide is responsible for the attenuation in alpha adrenergic receptor responsiveness. PURPOSE: This study examined alpha adrenergic receptor responsiveness under normal conditions and in the presence of nitric oxide synthase blockade. The hypothesis was that the attenuation in alpha adrenergic receptor responsiveness would be abolished by inhibition of nitric oxide production. METHODS: Ten mongrel dogs were instrumented chronically with flowprobes on the external iliac arteries of both hindlimbs and a catheter in one femoral artery. Under control conditions and after nitric oxide synthase blockade with L-NAME (15 mg/kg) phenylephrine (alpha 1 agonist) and clonidine (alpha 2 agonist) were infused individually as a bolus into the femoral artery catheter at rest (R) and during mild (M, 3 miles/h), and heavy exercise (H, 6 miles/h 10% grade). RESULTS: Intraarterial infusions of phenylephrine reduced external iliac vascular conductance before (R = -91 ± 3%, M = -80 ± 5%, H = -75 ± 6%) and after (R = -85 ± 5%, M = -85 ± 5%, H = -84 ± 5%) administration of L-NAME. Intraarterial infusions of clonidine also reduced external iliac vascular conductance before (R = -65 ± 6%, M = -39 ± 4%, H = -30 ± 3% and after (R = -67 ± 5%, M = -45 ± 3%, H = -35 ± 3%) administration of L-NAME. CONCLUSION: As expected, intraarterial infusions of phenylephrine and clonidine produced vasoconstriction that was attenuated during exercise compared to rest. Inhibition of the production of nitric oxide did abolish the attenuation in vasoconstriction seen with intraarterial infusions of phenylephrine. However, the attenuation observed with intraarterial infusions of clonidine was unaffected by nitric oxide synthase blockade. These results suggest that nitric oxide production plays a role in the attenuation of alpha1 adrenergic receptor responsiveness during exercise compared to rest. In contrast, the attenuation of alpha2 adrenergic receptor responsiveness during exercise does not appear to be mediated by the production of nitric oxide. Supported by NHLBI and VA.