Upregulation Of Inducible Nitric Oxide Synthase Contributes To Attenuated Cutaneous Vasodilation 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 is a proinflammatory, proconstrictor disease coinciding with endothelial dysfunction and inward vessel remodeling. Using the skin circulation, our aim was to determine whether inducible NO synthase (iNOS) upregulation attenuates NO-dependent cutaneous vasodilation in hypertensive humans. We hypothesized that, with hypertension, localized iNOS inhibition would restore vasodilation in response to NO-dependent stimuli, and iNOS expression would be increased and phosphorylated vasodilator-stimulated phosphoprotein would be decreased. For, in vivo protocols, 4 intradermal microdialysis fibers were placed in 9 hypertensive and 10 normotensive men and women (systolic blood pressure: 146±4 versus 113±2 mm Hg; P<0.001). Microdialysis fibers served as control, iNOS inhibited (1400 W), neuronal NO synthase inhibited (N?-propyl-l-arginine), and nonselective NOS inhibited (NG-nitro-l-arginine methyl ester). Cutaneous vascular conductance was calculated (percentage of sodium nitroprusside) during standardized local heating (42°C) and acetylcholine dose-response protocols (0.01, 0.10, 1.00, 5.00, 10.00, 50.00, 100.00 mmol/L). The NO-dependent local heating response was attenuated at control (95±2% versus 76±2% cutaneous vascular conductance; P<0.05) and neuronal NO synthase–inhibited sites (94±4% versus 77±3% cutaneous vascular conductance; P<0.01) in hypertensives. iNOS inhibition augmented the NO-dependent local heating response (93±2% versus 89±10% cutaneous vascular conductance). Acetylcholine-induced vasodilation was attenuated in control sites at doses =0.1 mmol/L of acetylcholine in hypertensives and was restored with iNOS inhibition (0.1 mmol/L, P<0.05; 1, 5, and 10 mmol/L, P<0.001; 50 and 100 mmol/L, P<0.01). In vitro iNOS expression was increased (P=0.006) and phosphorylated vasodilator-stimulated phosphoprotein was decreased in skin from hypertensive humans (P=0.04). These data suggest that iNOS is upregulated in essential hypertensive humans and contributes to reduced NO-dependent cutaneous vasodilation.

Additional Information

Caroline J. Smith, Lakshmi Santhanam, Rebecca S. Bruning, Anna Stanhewicz, Dan E. Berkowitz, & Lacy A. Holowatz (2011). Upregulation of Inducible Nitric Oxide Synthase Contributes to Attenuated Cutaneous Vasodilation in Essential Hypertensive Humans. Hypertension, 2011; 58:935–942. https://doi.org/10.1161/HYPERTENSIONAHA.111.178129. Publisher version of record available at: https://www.ahajournals.org/doi/10.1161/HYPERTENSIONAHA.111.178129
Language: English
Date: 2011
NO, inducible NO synthase, skin blood flow, hypertension, microvascular dysfunction

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