Rho-Kinase Activity And Cutaneous Vasoconstriction Is Upregulated In Essential Hypertensive Humans

ASU Author/Contributor (non-ASU co-authors, if there are any, appear on document)
Caroline Smith, Assistant Professor (Creator)
Appalachian State University (ASU )
Web Site: https://library.appstate.edu/

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 skin from HT humans. Four microdialysis fibers were placed in the forearm of 9 pre- to stage I hypertensive (MAP: 106 ± 3 mmHg) and 11 normotensive (NT; 86 ± 1 mmHg) men and women: Ringers (control), 3 mM fasudil (ROCK inhibited), 5 mM yohimbine + 1 mM proprananol (a- and ß-adrenoceptor inhibited; Y + P), Y + P + 3 mM fasudil (ROCK and adrenocepor inhibited). Skin blood flow was measured during local cooling (Tskl 24°C) and ROCK activity in skin biopsy samples was determined with western blot. In vitro phosphorylated myosin phosphatase target subunit 1 (pMYPT-1)/ROCK was increased in HT skin samples (p=0.0018). Functionally, no difference in basal vasomotor tone (Tskl 34°C) was observed between 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 (1–5 min; HT: -0.8±0.2 versus NT: -0.3±0.2 ?CVC baseline 1; P<0.0001) and late (36–40 min; HT: -0.9±0.1 versus NT: -0.5±0.2 ?CVC 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, ROCKactivity is increased and functional vasoconstriction is increasingly dependent upon Rho/ROCK mechanisms with essential hypertension.

Additional Information

Smith, C., Santhanam, L., and Alexander, L. (2013). Rho-Kinase Activity And Cutaneous Vasoconstriction Is Upregulated In Essential Hypertensive Humans. Microvasc Res. 2013 May ; 87: 58–64. doi:10.1016/j.mvr.2013.02.005. Publisher version of record available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4517969/
Language: English
Date: 2013
Rho-Kinase, cutaneous vasoconstriction, pre-hypertension, hypertension, microvascular dysfunction, superoxide, nitric oxide

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