Δευτέρα 24 Οκτωβρίου 2016

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

β-adrenergic receptor agonists such as isoproterenol can induce cutaneous vasodilatation and sweating in humans, however, the mechanisms underpinning this response remains unresolved. We evaluated the hypotheses that 1) nitric oxide synthase (NOS) contributes to β-adrenergic cutaneous vasodilatation, whereas cyclooxygenase (COX) limits the vasodilatation, and 2) COX contributes to β-adrenergic sweating. In 10 young males (25 ± 5 years), cutaneous vascular conductance (CVC) and sweat rate were evaluated at four intradermal forearm skin sites infused with 1) lactated Ringer's (control), 2) 10 mm L-NNA, a non-specific NOS inhibitor, 3) 10 mM ketorolac, a non-specific COX inhibitor, or 4) a combination of L-NNA and ketorolac. All sites were co-administered with a high dose isoproterenol (100 μM) for 3 min to maximally induce β-adrenergic sweating (β-adrenergic sweating is significantly blunted by subsequent activations). Approximately 60 min after washout period, three incremental doses of isoproterenol were co-administered (1, 10, 100 μM each for 25 min). Increases in CVC induced by the first and second 100 μM 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 P≤0.05). Ketorolac alone augmented increases in CVC induced by 10 and second 100 μM isoproterenol (both P≤0.05). 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 3-min 100 μM isoproterenol (P = 0.05). We show that while NOS contributes to β-adrenergic cutaneous vasodilatation, COX restrains the vasodilatation. Finally, combined inhibition of NOS and COX augments β-adrenergic sweating. (248/250)

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