Nitric oxide synthase and cyclooxygenase modulate -adrenergic cutaneous vasodilatation and sweating in young men

摘要

beta-Adrenergic receptor agonists such as isoproterenol can induce cutaneous vasodilatation and sweating in humans, but the mechanisms underpinning this response remain unresolved. We evaluated the hypotheses that (1) nitric oxide synthase (NOS) contributes to -adrenergic cutaneous vasodilatation, whereas cyclooxygenase (COX) limits the vasodilatation, and (2) COX contributes to -adrenergic sweating. In 10 young males (255years), cutaneous vascular conductance (CVC) and sweat rate were evaluated at four intradermal forearm skin sites infused with (1) lactated Ringer solution (control), (2) 10mmN-nitro-l-arginine (l-NNA), a non-specific NOS inhibitor, (3) 10mm ketorolac, a non-specific COX inhibitor, or (4) a combination of l-NNA and ketorolac. All sites were co-administered with a high dose of isoproterenol (100m) for 3min to maximally induce -adrenergic sweating (-adrenergic sweating is significantly blunted by subsequent activations). Approximately 60min after the washout period, three incremental doses of isoproterenol were co-administered (1, 10 and 100m each for 25min). Increases in CVC induced by the first and second 100m isoproterenol were attenuated by l-NNA alone, and those in response to all doses of isoproterenol were reduced by l-NNA with co-infusion of ketorolac (all P0.05). Ketorolac alone augmented increases in CVC induced by 10m and by the second 100m isoproterenol (both P0.05). While isoproterenol-induced sweating was not affected by the separate administration of l-NNA or ketorolac (all P>0.05), their combined administration augmented sweating elicited by the first 3min of 100m isoproterenol (P=0.05). We show that while NOS contributes to -adrenergic cutaneous vasodilatation, COX restrains the vasodilatation. Finally, combined inhibition of NOS and COX augments -adrenergic sweating.