Rho-Kinase activity and cutaneous vasoconstriction is upregulated in essential hypertensive humans

Caroline J. Smith, Lakshmi Santhanam, Lacy M. Alexander

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)58-64
Number of pages7
JournalMicrovascular Research
Volume87
DOIs
StatePublished - May 1 2013

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rho-Associated Kinases
Vasoconstriction
Cooling
Skin
Hypertension
Myosin-Light-Chain Phosphatase
Yohimbine
Biopsy
Adrenergic Receptors
Microdialysis
Forearm
Blood
Western Blotting
Fibers

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Cardiology and Cardiovascular Medicine
  • Cell Biology

Cite this

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title = "Rho-Kinase activity and cutaneous vasoconstriction is upregulated in essential hypertensive humans",
abstract = "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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Rho-Kinase activity and cutaneous vasoconstriction is upregulated in essential hypertensive humans. / Smith, Caroline J.; Santhanam, Lakshmi; Alexander, Lacy M.

In: Microvascular Research, Vol. 87, 01.05.2013, p. 58-64.

Research output: Contribution to journalArticle

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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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