RESUMO
Patients with coronary artery disease have attenuated coronary vasodilator responses to physiological stress, which is partially attributed to a ß-adrenergic receptor (ß-AR)-mediated mechanisms. Whether ß-ARs contribute to impaired coronary vasodilation seen with healthy aging is unknown. The purpose of this study was to investigate the role of ß-ARs in coronary exercise hyperemia in healthy humans. Six young men (26 ± 1 yr) and seven older men (67 ± 4 yr) performed isometric handgrip exercise at 30% maximal voluntary contraction for 2 min after receiving intravenous propranolol, a ß-AR antagonist, and no treatment. Isoproterenol, a ß-AR agonist, was infused to confirm the ß-AR blockade. Blood pressure and heart rate were monitored continuously, and coronary blood flow velocity (CBV, left anterior descending artery) was measured by transthoracic Doppler echocardiography. Older men had an attenuated ΔCBV to isometric exercise (3.8 ± 1.3 vs. 9.7 ± 2.1 cm/s, P = 0.02) compared with young men. Propranolol decreased the ΔCBV at peak handgrip exercise in young men (9.7 ± 2.1 vs. 2.7 ± 0.9 cm/s, P = 0.008). However, propranolol had no effect on ΔCBV in older men (3.8 ± 1.3 vs. 4.2 ± 1.9 cm/s, P = 0.9). Older men also had attenuated coronary hyperemia to low-dose isoproterenol. These data indicate that ß-AR control of coronary blood flow is impaired in healthy older men.
Assuntos
Antagonistas Adrenérgicos beta/administração & dosagem , Envelhecimento , Vasos Coronários/efeitos dos fármacos , Exercício Físico , Hiperemia/fisiopatologia , Propranolol/administração & dosagem , Vasodilatação/efeitos dos fármacos , Agonistas Adrenérgicos beta/administração & dosagem , Adulto , Fatores Etários , Idoso , Vasos Coronários/fisiopatologia , Estudos Cross-Over , Ecocardiografia Doppler , Força da Mão , Voluntários Saudáveis , Humanos , Infusões Intravenosas , Contração Isométrica , Isoproterenol/administração & dosagem , Masculino , Pessoa de Meia-IdadeRESUMO
In response to hypoxia, a net vasodilation occurs in the limb vasculature in young healthy humans and this is referred to as "hypoxia-induced vasodilation". We performed two separate experiments to determine (1) if hypoxia-induced forearm vasodilation is impaired in older men (n = 8) compared to young men (n = 7) and (2) if acute systemic infusion of ascorbic acid would enhance hypoxia-induced vasodilation in older men (n = 8). Heart rate, mean arterial pressure, oxygen saturation, minute ventilation, forearm vascular conductance (FVC, Doppler ultrasound), and cutaneous vascular conductance (CVC, laser Doppler flowmetry) were recorded continuously while subjects breathed 10% oxygen for 5 min. Changes from baseline were compared between groups and between treatments. The older adults had a significantly attenuated increase in FBF (13 ± 4 vs. 30 ± 7%) and FVC (16 ± 4 vs. 30 ± 7%) in response to 5 min of hypoxia. However, skin blood flow responses were comparable between groups (young: 35 ± 9, older: 30 ± 6%). In Experiment 2, FVC responses to 5 min of breathing 10% oxygen were not significantly different following saline (3 ± 10%) and ascorbic acid (8 ± 10%) in the older men. Ascorbic acid also had no physiological effects in the young men. These findings advance our basic understanding of how aging influences vascular responses to hypoxia and suggest that, in healthy humans, hypoxia-induced vasodilation is not restrained by reactive oxygen species.