Journal
JOURNAL OF PHYSIOLOGY-LONDON
Volume 581, Issue 2, Pages 863-872Publisher
WILEY
DOI: 10.1113/jphysiol.2007.128959
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Funding
- NCRR NIH HHS [M01 RR010732, M01-RR10732] Funding Source: Medline
- NIA NIH HHS [R01-AG07004-17, R01 AG007004] Funding Source: Medline
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Reflex cutaneous vasodilatation is dependent on nitric oxide (NO), which is diminished in hypertension (HTN). Arginase may be up-regulated with HTN, which preferentially metabolizes L-arginine (L-arg), competing with NO-synthase (NOS)-mediated pathways and limiting NO synthesis. We hypothesized that NO-dependent vasodilatation would be attenuated in HTN skin, and arginase inhibition (A-I) alone or with concurrent L-arginine supplementation, would augment vasodilatation. Five microdialysis fibres were placed in skin of eight unmedicated subjects with HTN (mean arterial pressure (MAP), 112 +/- 1 mmHg) and nine age-matched normotensive (AMN) (MAP: 87 +/- 1 mmHg) men and women to serve as: control (C, Ringer solution), NOS inhibited (NOS-I, 10 mM L-NAME), A-I (5 mM BEC + 5 mM nor-NOHA), L-arg supplemented (L-arg, 10 mM L-arg), and combined A-I + L-arg. Reflex vasodilatation was induced by using a water-perfused suit to increase oral temperature (T-or) 1.0 degrees C. Red cell flux was measured by laser-Doppler flowmetry over each site. Cutaneous vascular conductance was calculated (CVC = flux/MAP) and normalized to maximal CVC (28 mM SNP + local heating to 43 degrees C). The Delta%CVCmax between the control and NOS-I site was calculated as the difference between C and NOS-I sites. Maximal CVC was attenuated in the HTN subjects by similar to 25% compared with AMN subjects (P < 0.001). Throughout, whole body heating %CVCmax was not different between the groups (HTN, 43 +/- 3%CVCmax versus AMN, 45 +/- 3%CVCmax, P > 0.05). NOS-I significantly decreased %CVCmax in both groups but %CVCmax was greater in the HTN group (HTN, 32 +/- 4%CVCmax versus AMN, 23 +/- 3%CVCmax, P < 0.05). The Delta%CVCmax between the control and NOS-I sites was attenuated at Delta T-or > 0.5 degrees C in the HTN group (P < 0.001 versus AMN). A-I alone augmented %CVCmax only in the HTN group (HTN, 65 +/- 5%CVCmax versus AMN, 48 +/- 3%CVCmax, P < 0.05). L-Arg alone did not affect %CVCmax in either group (HTN, 49 +/- 5%CVCmax versus AMN, 49 +/- 3%CVCmax, P > 0.05). Combined A-I + L-arg augmented %CVCmax in both subject groups compared with their respective control sites (HTN, 60 +/- 7%CVCmax versus AMN, 61 +/- 3%CVCmax, both P < 0.05 versus respective control sites). Vasodilatation is attenuated with HTN due to decreased NO-dependent vasodilatation and can be augmented with arginase inhibition but not L-arg supplementation, suggesting that arginase is up-regulated with HTN.
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