Misregulation of the arginase pathway in tissues of spontaneously hypertensive rats.
There is a growing evidence that arginase has a role in the pathophysiology of cardiovascular diseases including hypertension. We recently reported arginase upregulation in aortas from hypertensive spontaneously hypertensive rats (SHRs). The aim of this study was to determine whether arginase abnormalities occur in other tissues of SHR, including the target organs of hypertension. Experiments were conducted on 5-, 10-, 19- and 26-week-old SHRs and Wistar-Kyoto (WKY) rats. Arginase activity and expression were evaluated in heart, kidney, liver, lung and brain tissue extracts. To investigate the role of blood pressure by itself in arginase abnormalities, arginase activity was determined in 10-week-old SHRs previously treated with hydralazine (20 mg kg(-1) per day, for 5 weeks). Compared with WKY rats, cardiac arginase activity was higher in hypertensive SHRs aged 10 weeks (+46%, P<0.05), 19 weeks (+29%, P<0.05) and 26 weeks (+23%, NS). Similar results were found in lungs in which arginase activity was increased in SHRs aged 10 weeks (+39%, P<0.05), 19 weeks (+49%, P<0.05) and 26 weeks (+36%, P<0.05) compared with WKY rats. The changes in arginase activity in these tissues were not associated with changes in enzyme expression. The prevention of hypertension by hydralazine blunted the increase in arginase activity in the hearts but not in the lungs. No change in arginase activity/expression was found in the kidney, liver or brain. In conclusion, this study shows that increased arginase activity is not restricted to large vessels in SHRs and suggests that cardiac arginase activity is hemodynamic sensitive.
Bagnost
Teddy
T
Laboratoire de Physiologie-Pharmacologie-Nutrition Préventive Expérimentale, Besancon, France.
Berthelot
Alain
A
Alvergnas
Magalie
M
Miguet-Alfonsi
Carole
C
André
Claire
C
Guillaume
Yves
Y
Demougeot
Céline
C
D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D001119:Arginase / Q000378:metabolism*; D001794:Blood Pressure / Q000502:physiology*; D001835:Body Weight / Q000502:physiology; D001921:Brain / Q000201:enzymology; D004789:Enzyme Activation / Q000187:drug effects; D006339:Heart Rate / Q000502:physiology; D006830:Hydralazine / Q000494:pharmacology; D006973:Hypertension / Q000188:drug therapy / Q000378:metabolism*; D007668:Kidney / Q000201:enzymology; D008099:Liver / Q000201:enzymology; D008168:Lung / Q000201:enzymology; D008297:Male; D009206:Myocardium / Q000201:enzymology*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY
D000959:Antihypertensive Agents; D006830:Hydralazine; C113162:Arg2 protein, rat; D001119:Arginase; C542908:arginase I, rat