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Age‐ and Sex‐Related Differences in the Cutaneous Vascular Response to Exogenous Angiotensin II
Author(s) -
Krajek Alex C,
Kolb Kelsey E,
Lang James A
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.lb684
Subject(s) - angiotensin ii , vasoconstriction , microdialysis , endocrinology , medicine , chemistry , propranolol , yohimbine , vasodilation , receptor , antagonist , central nervous system
The enzymatic machinery for the production and activation of angiotensin II (AngII) is locally expressed in human skin. Moreover, it has been demonstrated that AngII contributes to the reflex vasoconstriction (VC) response in aged skin; however, the cutaneous responsivity of AngII across a range of doses has not been examined. Thus, we hypothesized that the cutaneous VC response will incrementally increase with higher doses of Ang II. Additionally, we hypothesized that AngII‐mediated VC will be affected by the inhibition of adrenoreceptor or angiotensin II type II receptor (AT 2 R) pathways. Three microdialysis (MD) fibers were placed in the forearm skin of 8 young (Y: 23 ± 1 year) and 8 older (O: 68 ± 1 year) individuals for administration of 1) lactated Ringer's solution (control), 2) adrenoreceptor blockade with 5mM yohimbine + 1 mM propranolol (Y+P), and 3) AT 2 R inhibition with 1 μM PD‐123319 (PD). Then, AngII was added to the perfusates at eight graded dose concentrations, ranging from 0.1 nM to 1 mM, administered at 10 min intervals. Laser Doppler flux (LDF) was measured for each MD site and cutaneous vascular conductance (CVC) was calculated as CVC = LDF/mean arterial pressure and was expressed as a percent change from baseline (%ΔCVC). Compared to the control site (Y = 31 ± 6, O = 36 ± 5 %ΔCVC), the peak VC response at the highest dose was attenuated at the Y+P site (Y = 20 ± 5%, O = 32 ± 6 %ΔCVC) but was elevated at the PD site (Y = 42 ± 10, O = 41 ± 5 %ΔCVC). Furthermore, older women (44 ± 5 %ΔCVC) exhibited a greater peak VC at the control site compared to older men (23 ± 5 %ΔCVC; p < 0.05). These results indicate that older women have greater vasoconstrictor sensitivity to exogenous AngII than young individuals or older men. These data further suggest that AngII may be affecting multiple targets, including adrenergic and AT 2 R pathways. Support or Funding Information DMU IOER Grant 05‐13‐05