1: Am J Physiol Regul Integr Comp Physiol. 2005 Apr;288(4):R1057-62. Epub 2004
Dec 9. 

Arginase inhibition restores arteriolar endothelial function in Dahl rats with
salt-induced hypertension.

Johnson FK, Johnson RA, Peyton KJ, Durante W.

Tulane Hypertension and Renal Center of Excellence, Department of Physiology,
Tulane University Health Sciences Center, New Orleans, Louisiana, USA.

Vascular tissues express arginase that metabolizes L-arginine to L-ornithine and
urea and thus reduces substrate availability for nitric oxide formation. Dahl
salt-sensitive (Dahl-S) rats with salt-induced hypertension show endothelial
dysfunction, including decreased vascular nitric oxide formation. This study
tests the hypothesis that increased vascular arginase activity contributes to
endothelial dysfunction in hypertensive Dahl-S rats. Male Dahl-S rats (5-6 wk)
were placed on high (8%) or low (0.3%) NaCl diets for 4 wk. With respect to the
low-salt group, mean arterial blood pressure was increased in the high-salt
animals. Immunohistochemical stainings for arginase I and II were enhanced in
arterioles isolated from high-salt Dahl-S rats. Experiments used isolated Krebs
buffer-superfused first-order gracilis muscle arterioles with constant pressure
(80 mmHg) and no luminal flow or constant midpoint but altered endpoint
pressures to establish graded levels of luminal flow (0-50 microl/min). In
high-salt arterioles, responses to an endothelium-dependent vasodilator
acetylcholine (1 nmol/l to 3 micromol/l) and flow-induced dilation were
decreased. Acute in vitro treatment with an inhibitor of arginase, 100
micromol/l (S)-(2-boronoethyl)-L-cystine, or the nitric oxide precursor, 1
mmol/l L-arginine, similarly enhanced acetylcholine and flow-induced maximal
dilations and abolished the differences between high- and low-salt arterioles.
These data show that arteriolar arginase expression is increased and that
endothelium-dependent vasodilation is decreased in high-salt Dahl-S rats. Acute
pretreatment with an arginase inhibitor or with L-arginine restores
endothelium-dependent vasodilation and abolishes the differences between high-
and low-salt groups. These results suggest that enhanced vascular arginase
activity contributes to endothelial dysfunction in Dahl-S rats with salt-induced
hypertension and identifies arginase as a potential therapeutic target to
prevent endothelial dysfunction.

PMID: 15591155 [PubMed - indexed for MEDLINE]