There is growing evidence that vascular
arginase plays a role in pathophysiology of
vascular diseases. We recently reported high
arginase activity/expression in young adult hypertensive spontaneously hypertensive rats (SHR). The aim of the present study was to characterize the time course of
arginase pathway abnormalities in SHR and to explore the contributing role of hemodynamics and
inflammation. Experiments were conducted on 5, 10, 19 and 26-week-old SHR and their age-matched control Wistar Kyoto (WKY) rats.
Arginase activity as well as expression of
arginase I,
arginase II, endothelial and inducible NOS were determined in aortic
tissue extracts. Levels of
L-arginine, NO catabolites and
IL-6 (a marker of
inflammation) were measured in plasma.
Arginase activity/expression was also measured in 10-week-old SHR previously treated with
hydralazine (20 mg/kg/day, per os, for 5 weeks). As compared to WKY, SHR exhibited high vascular
arginase I and II expression from prehypertensive to established stages of
hypertension. However, a mismatch between expression and activity was observed at the prehypertensive stage.
Arginase expression was not related either to plasma
IL-6 levels or to expression of NOS. Prevention of
hypertension by
hydralazine significantly blunted
arginase upregulation and restored
arginase activity. Importantly,
arginase activity and blood pressure (BP) correlated in SHR. In conclusion, our results demonstrate that
arginase upregulation precedes blood pressure rising and identify elevated blood pressure as a contributing factor of
arginase dysregulation in genetic
hypertension. They also demonstrated a close relationship between
arginase activity and BP, thus making
arginase a promising target for
antihypertensive therapy.