Time course of vascular arginase expression and activity in spontaneously hypertensive rats.
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.
Demougeot
Céline
C
Laboratoire de Physiologie, Pharmacologie, Nutrition Préventive Expérimentale, Equipe Optimisation Métabolique et Cellulaire, 25030 Besancon, France. cdemouge@univ-fcomte.fr
Prigent-Tessier
Anne
A
Bagnost
Teddy
T
André
Claire
C
Guillaume
Yves
Y
Bouhaddi
Malika
M
Marie
Christine
C
Berthelot
Alain
A
D000818:Animals; D000959:Antihypertensive Agents / Q000627:therapeutic use; D001013:Aorta, Thoracic / Q000201:enzymology*; D001119:Arginase / Q000096:biosynthesis*; D001120:Arginine / Q000097:blood; D001794:Blood Pressure / Q000502:physiology; D001835:Body Weight / Q000502:physiology; D006830:Hydralazine / Q000627:therapeutic use; D006973:Hypertension / Q000097:blood / Q000201:enzymology* / Q000503:physiopathology / Q000517:prevention & control; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D009569:Nitric Oxide / Q000097:blood / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000096:biosynthesis; D052250:Nitric Oxide Synthase Type III / Q000096:biosynthesis; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D013997:Time Factors
D000959:Antihypertensive Agents; D015850:Interleukin-6; D006830:Hydralazine; D009569:Nitric Oxide; D001120:Arginine; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; D001119:Arginase