Hypertension Research Today is a free monthly online journal that collates and summarizes the latest research about Hypertension, including details on symptoms, diagnosis, diet, treatment, causes.

Up-regulation of arginase activity contributes to attenuated reflex cutaneous vasodilatation in hypertensive humans.

Holowatz LA, Kenney WL

Pennsylvania State University, Noll Laboratory, Department of Kinesiology, University Park, PA 16802, USA. lma191@psu.edu

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%CVC(max) 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 approximately 25% compared with AMN subjects (P<0.001). Throughout, whole body heating %CVC(max) was not different between the groups (HTN, 43 +/- 3%CVC(max) versus AMN, 45 +/- 3%CVC(max), P>0.05). NOS-I significantly decreased %CVC(max) in both groups but %CVC(max) was greater in the HTN group (HTN, 32 +/- 4%CVC(max) versus AMN, 23 +/- 3%CVC(max), P<0.05). The Delta%CVC(max) between the control and NOS-I sites was attenuated at DeltaT(or) > 0.5 degrees C in the HTN group (P < 0.001 versus AMN). A-I alone augmented %CVC(max) only in the HTN group (HTN, 65 +/- 5%CVC(max) versus AMN, 48 +/- 3%CVC(max), P<0.05). L-Arg alone did not affect %CVC(max) in either group (HTN, 49 +/- 5%CVC(max) versus AMN, 49 +/- 3%CVC(max), P > 0.05). Combined A-I + L-arg augmented %CVC(max) in both subject groups compared with their respective control sites (HTN, 60 +/- 7%CVC(max) versus AMN, 61 +/- 3%CVC(max), 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.

Published 4 June 2007 in J Physiol, 581: 863-72.
Full-text of this article is available online (may require subscription).

© 2004-2008 Hypertension Research Today. All Rights Reserved.