RESUMO
Previous studies indicate that sex-related differences exist in the regulation of cutaneous vasodilation, however, the mechanisms remain unresolved. We assessed if sex-differences in young adults exist for cholinergic, nicotinic, and ß-adrenergic cutaneous vasodilation with a focus on nitric oxide synthase (NOS), cyclooxygenase (COX), and K+ channel mechanisms. In twelve young men and thirteen young women, four intradermal forearm skin sites were perfused with the following: 1) lactated Ringer's solution (control), 2) 10 mM Nω-nitro-l-arginine, a non-selective NOS inhibitor, 3) 10 mM ketorolac, a non-selective COX inhibitor, or 4) 50 mM BaCl2, a nonspecific K+ channel blocker. At all four sites, cutaneous vasodilation was induced by 1) 10 mM nicotine, a nicotinic receptor agonist, 2) 100 µM isoproterenol, a nonselective ß-adrenergic receptor agonist, and 3) 2 mM and 2000 mM acetylcholine, an acetylcholine receptor agonist. Nicotine and isoproterenol were administered for 3 min, whereas each acetylcholine dose was administered for 25 min. Regardless of treatment site, cutaneous vasodilation in response to nicotine and a high dose of acetylcholine (2000 mM) were lower in women than men. By contrast, isoproterenol induced cutaneous vasodilation was greater in women vs. men. Irrespective of sex, NOS inhibition or K+ channel blockade attenuated isoproterenol-mediated cutaneous vasodilation, whereas K+ channel blockade decreased nicotine-induced cutaneous vasodilation. Taken together, our findings indicate that while the mechanisms underlying cutaneous vasodilation are comparable between young men and women, sex-related differences in the magnitude of cutaneous vasodilation do exist and this response differs as a function of the receptor agonist.
Assuntos
Vasos Sanguíneos/enzimologia , Óxido Nítrico Sintase/metabolismo , Canais de Potássio/metabolismo , Prostaglandina-Endoperóxido Sintases/metabolismo , Receptores Adrenérgicos beta/metabolismo , Receptores Colinérgicos/metabolismo , Pele/irrigação sanguínea , Vasodilatação , Agonistas Adrenérgicos beta/farmacologia , Adulto , Vasos Sanguíneos/efeitos dos fármacos , Agonistas Colinérgicos/farmacologia , Inibidores de Ciclo-Oxigenase/farmacologia , Feminino , Antebraço , Humanos , Masculino , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase/antagonistas & inibidores , Bloqueadores dos Canais de Potássio/farmacologia , Canais de Potássio/efeitos dos fármacos , Receptores Nicotínicos/metabolismo , Fatores Sexuais , Transdução de Sinais , Vasodilatação/efeitos dos fármacos , Adulto JovemRESUMO
NEW FINDINGS: What is the central question of this study? We evaluated whether regional variations exist in NO-dependent cutaneous vasodilatation and sweating during cholinergic stimulation. What is the main finding and its importance? Peak cutaneous vasodilatation and sweating were greater on the torso than the forearm. Furthermore, we found that NO was an important modulator of cholinergic cutaneous vasodilatation, but not sweating, across body regions, with a greater contribution of NO to cutaneous vasodilatation in the limb compared with the torso. These findings advance our understanding of the mechanisms influencing regional variations in cutaneous vasodilator and sweating responses to pharmacological stimulation. ABSTRACT: Regional variations in cutaneous vasodilatation and sweating exist across the body. Nitric oxide (NO) is an important modulator of these heat loss responses in the forearm. However, whether regional differences in NO-dependent cutaneous vasodilatation and sweating exist remain uncertain. In 14 habitually active young men (23 ± 4 years of age), cutaneous vascular conductance (CVC%max ) and local sweat rates were assessed at six skin sites. On each of the dorsal forearm, chest and upper back (trapezius), sites were continuously perfused with either lactated Ringer solution (control) or 10 mm Nω -nitro-l-arginine (l-NNA; an NO synthase inhibitor) dissolved in Ringer solution, via microdialysis. At all sites, cutaneous vasodilatation and sweating were induced by co-administration of the cholinergic agonist methacholine (1, 10, 100, 1000 and 2000 mm; 25 min per dose) followed by 50 mm sodium nitroprusside (20-25 min) to induce maximal vasodilatation. The l-NNA attenuated CVC%max relative to the control conditions for all regions (all P < 0.05), and NO-dependent vasodilatation was greater at the forearm compared with the back and chest (both P < 0.05). Furthermore, maximal vasodilatation was higher at the back and chest relative to the forearm (both P < 0.05). Conversely, l-NNA had negligible effects on sweating across the body (all P > 0.05). Peak local sweat rate was higher at the back relative to the forearm (P < 0.05), with a similar trend observed for the chest. In habitually active young men, NO-dependent cholinergic cutaneous vasodilatation varied across the body, and the contribution to cholinergic sweating was negligible. These findings advance our understanding of the mechanisms influencing regional variations in cutaneous vasodilatation and sweating during pharmacological stimulation.
Assuntos
Agonistas Muscarínicos/administração & dosagem , Óxido Nítrico Sintase/antagonistas & inibidores , Óxido Nítrico Sintase/metabolismo , Pele/enzimologia , Sudorese/fisiologia , Vasodilatação/fisiologia , Adulto , Relação Dose-Resposta a Droga , Inibidores Enzimáticos/administração & dosagem , Humanos , Injeções Subcutâneas , Masculino , Cloreto de Metacolina/administração & dosagem , Nitroarginina/administração & dosagem , Pele/irrigação sanguínea , Pele/efeitos dos fármacos , Sudorese/efeitos dos fármacos , Vasodilatação/efeitos dos fármacos , Adulto JovemRESUMO
OBJECTIVES: Heat shock protein 90 (HSP90) contributes to cutaneous vasodilatation during exercise in the heat through nitric oxide (NO) synthase (NOS)-dependent mechanisms in young adults. We hypothesized that similar responses would be observed in older middle-aged adults. METHODS: In nineteen habitually active older middle-aged (56 ± 5 years) men (n = 9) and women (n = 10), cutaneous vascular conductance (CVC) was measured at four forearm skin sites continuously treated with (a) lactated Ringers solution (Control), (b) 10 mmol/L L-NAME (NOS inhibitor), (c) 178 µmol/L geldanamycin (HSP90 inhibitor), or (d) 10 mmol/L L-NAME and 178 µmol/L geldanamycin combined. Participants rested in an upright semi-recumbent position in the heat (35°C) for 70 minutes, followed by a 50-minute bout of moderate-intensity cycling (~55% peak oxygen uptake) and a 30-minute recovery period in the heat. RESULTS: In both men and women, we observed no significant effects of HSP90 inhibition on CVC throughout rest, exercise, and recovery in the heat (all P > 0.27). Conversely, NOS inhibition and dual NOS and HSP90 inhibition attenuated CVC relative to Control throughout the protocol (all P ≤ 0.05). CONCLUSIONS: While NOS mediates cutaneous vasodilatation during rest, exercise, and recovery in the heat, HSP90 does not measurably influence this response in habitually active older middle-aged men or women under these conditions.