Reflex vasoconstriction in aged human skin increasingly relies on Rho kinase-dependent mechanisms during whole body cooling

James A. Lang, John D. Jennings, Lacy A. Holowatz, W. Larry Kenney

Research output: Contribution to journalArticlepeer-review

22 Scopus citations

Abstract

Primary human aging may be associated with augmented Rho kinase (ROCK)-mediated contraction of vascular smooth muscle and ROCK-mediated inhibition of nitric oxide synthase (NOS). We hypothesized that the contribution of ROCK to reflex vasoconstriction (VC) is greater in aged skin. Cutaneous VC was elicited by 1) whole body cooling [mean skin temperature (Tsk) = 30.5°C] and 2) local norepinephrine (NE) infusion (1 × 10-6 M). Four microdialysis fibers were placed in the forearm skin of eight young (Y) and eight older (O) subjects for infusion of 1) Ringer solution (control), 2) 3 mM fasudil (ROCK inhibition), 3) 20 mM NG-nitro-L-arginine methyl ester (NOS inhibition), and 4) both ROCK + NOS inhibitors. Red cell flux was measured by laser-Doppler flowmetry over each site. Cutaneous vascular conductance (CVC) was calculated as flux/mean arterial pressure and normalized to baseline CVC (%ΔCVCbaseline). VC was reduced at the control site in O during cooling (Y, -34 ± 3; and O, -18 ± 3%ΔCVCbaseline; P < 0.001) and NE infusion (Y, -53 ± 4, and O, -41 ± 9%ΔCVCbaseline; P = 0.006). Fasudil attenuated VC in both age groups during mild cooling; however, this reduction remained only in O but not in Y skin during moderate cooling (Y, -30 ± 5; and O, -7 ± 1%ΔCVCbaseline; P = 0.016) and was not altered by NOS inhibition. Fasudil blunted NE-mediated VC in both age groups (Y, -23 ± 4; and O, -7 ± 3%ΔCVCbaseline; P < 0.01). Cumulatively, these data indicate that reflex VC is more reliant on ROCK in aged skin such that approximately half of the total VC response to whole body cooling is ROCK dependent.

Original languageEnglish (US)
Pages (from-to)H1792-H1797
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume297
Issue number5
DOIs
StatePublished - Nov 2009

All Science Journal Classification (ASJC) codes

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Fingerprint Dive into the research topics of 'Reflex vasoconstriction in aged human skin increasingly relies on Rho kinase-dependent mechanisms during whole body cooling'. Together they form a unique fingerprint.

Cite this