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

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

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

Lacy A Holowatz,W Larry Kenney,

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.

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

LA Holowatz,WL Kenney,

For similar vasodilation research abstracts see: vasodilation research

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

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: The Journal of physiology

VOLUME: 581

Page Numbers: 863-72

Journal Abbreviation: J. Physiol. (Lond.)

ISSN: 0022-3751

DAY: 8

MONTH: 03

YEAR: 2007

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

Number of References:

LANGUAGE: eng

NlmUniqueID: 266262

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

KEYWORDS: Vasodilation

MESH TERMS: drug effects

Chemical & Substance for Abstract: Up-regulation of arginase activity contributes to attenuated reflex cutaneous vasodilatation in hypertensive humans. Information

Substance Name: Arginase

Registry Number: EC 3.5.3.1

Grant and Affiliation Information for Up-regulation of arginase activity contributes to attenuated reflex cutaneous vasodilatation in hypertensive humans.

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

Country: England

AGENCY: United States NIA

GRANT: R01-AG07004-17

ACRONYM: AG

MEDLINETA: J Physiol

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