Angiotensin II type I receptor blockade attenuates reflex cutaneous vasoconstriction in aged but not young skin

摘要

Stimulation of angiotensin II type I receptors (AT_1R) elicits vasoconstriction (VC) that may be occurring through the activation of a pathogenic vascular pathway such as Rho kinase (ROCK). We hypothesize that reflex cutaneous VC to whole body cooling (mean skin temperature = 30.5°C) in older humans relies in part on AT_1R activation, which may explain greater ROCK activity attendant with aging. Two microdialysis (MD) fibers were placed in the forearm skin of 10 young (Y; 24 ± 1 yr) and 10 older (O; 70 ± 2 yr) individuals for infusion of 1) lactated Ringer's solution (switched to fasudil, a ROCK antagonist, after cooling); and 2) AT_1R blockade with losartan. Laser Doppler flux (LDF) was measured over each MD site and cutaneous vascular conductance (CVC) was calculated (CVC = LDF/mean arterial pressure) and expressed as percent change from baseline (%ΔCVC_(BASELINE)). IN older individuals the VC response to whole body cooling was blunted (Y = -34 ± 2, O = -17 ± 3%ACVC) and was further attenuated at the losartan site (Y = -34 ± 3, O = -9 ± 3%ΔCVC; P < 0.05). The VC response to an exogenous 10-muM dose of angiotensin II (Y = -27 ± 3, O = -42 ± 5%ACVC) was completely blocked in sites pretreated with losartan or with fasudil. These data suggest that AT_1R activation contributes to the reflex VC response in aged but not young skin. Furthermore, the angiotensin II component of the VC response appears to occur primarily through a ROCK-mediated mechanism.