TY - JOUR
T1 - Rho-Kinase activity and cutaneous vasoconstriction is upregulated in essential hypertensive humans
AU - Smith, Caroline J.
AU - Santhanam, Lakshmi
AU - Alexander, Lacy M.
N1 - Funding Information:
This study was supported by the National Institutes of Health grant R01-HL093238-03 (to L.A.H.).
PY - 2013/5
Y1 - 2013/5
N2 - Essential hypertension (HT) is associated with endothelial dysfunction augmented vasoconstriction (VC) which may be secondary to increased Rho/Rho-Kinase (ROCK)-dependent mechanisms. Our aim was to assess the in vivo magnitude of cutaneous VC to local cooling as a ROCK specific stimulus, and in vitro evaluate ROCK activity in the skin from HT humans. Four microdialysis fibers were placed in the forearm of 9 pre- to stage I hypertensive (MAP: 106±3mm Hg) and 11 normotensive (NT; 86±1mm Hg) men and women: Ringers (control), 3mM fasudil (ROCK inhibited), 5mM yohimbine+1mM proprananol (α- and β-adrenoceptor inhibited; Y+P), Y+P+3mM fasudil (ROCK and adrenocepor inhibited). Skin blood flow was measured during local cooling (Tskl 24°C) and ROCK activity in the skin biopsy samples was determined with western blot. In vitro phosphorylated myosin phosphatase target subunit 1 (pMYPT-1)/ROCK was increased in the HT skin samples (p=0.0018). Functionally, no difference in basal vasomotor tone (Tskl 34°C) was observed between the groups (HT: 0.36±0.07 vs. NT: 0.31±0.07 CVC), nor at the control site during local cooling. Pre- to stage 1 hypertensives show greater ROCK-mediated vasoconstriction at early (1-5min; HT: -0.8±0.2 versus NT: -0.3±0.2 δCVC baseline 1; P<0.0001) and late (36-40min; HT: -0.9±0.1 versus NT: -0.5±0.2 δCVC baseline 1; P<0.0001) phases of local cooling. These data suggest that the magnitude of cutaneous vasoconstriction to local cooling does not differ in normotensive and pre- to stage I essential hypertensive humans; however, ROCK activity is increased and functional vasoconstriction is increasingly dependent upon Rho/ROCK mechanisms with essential hypertension.
AB - Essential hypertension (HT) is associated with endothelial dysfunction augmented vasoconstriction (VC) which may be secondary to increased Rho/Rho-Kinase (ROCK)-dependent mechanisms. Our aim was to assess the in vivo magnitude of cutaneous VC to local cooling as a ROCK specific stimulus, and in vitro evaluate ROCK activity in the skin from HT humans. Four microdialysis fibers were placed in the forearm of 9 pre- to stage I hypertensive (MAP: 106±3mm Hg) and 11 normotensive (NT; 86±1mm Hg) men and women: Ringers (control), 3mM fasudil (ROCK inhibited), 5mM yohimbine+1mM proprananol (α- and β-adrenoceptor inhibited; Y+P), Y+P+3mM fasudil (ROCK and adrenocepor inhibited). Skin blood flow was measured during local cooling (Tskl 24°C) and ROCK activity in the skin biopsy samples was determined with western blot. In vitro phosphorylated myosin phosphatase target subunit 1 (pMYPT-1)/ROCK was increased in the HT skin samples (p=0.0018). Functionally, no difference in basal vasomotor tone (Tskl 34°C) was observed between the groups (HT: 0.36±0.07 vs. NT: 0.31±0.07 CVC), nor at the control site during local cooling. Pre- to stage 1 hypertensives show greater ROCK-mediated vasoconstriction at early (1-5min; HT: -0.8±0.2 versus NT: -0.3±0.2 δCVC baseline 1; P<0.0001) and late (36-40min; HT: -0.9±0.1 versus NT: -0.5±0.2 δCVC baseline 1; P<0.0001) phases of local cooling. These data suggest that the magnitude of cutaneous vasoconstriction to local cooling does not differ in normotensive and pre- to stage I essential hypertensive humans; however, ROCK activity is increased and functional vasoconstriction is increasingly dependent upon Rho/ROCK mechanisms with essential hypertension.
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U2 - 10.1016/j.mvr.2013.02.005
DO - 10.1016/j.mvr.2013.02.005
M3 - Article
C2 - 23481864
AN - SCOPUS:84876340735
SN - 0026-2862
VL - 87
SP - 58
EP - 64
JO - Microvascular Research
JF - Microvascular Research
ER -