Arginase II knockout mouse displays a hypertensive phenotype despite a decreased vasoconstrictory profile.
Arginase upregulation is associated with aging and cardiovascular diseases. In this study we report on the cardiovascular phenotype of the arginase II knockout (KO) mouse. We demonstrate that vascular sensitivity and reactivity altered over time in these animals such that no influence on responses to vasoconstrictor activity was observed in 7-week-old KO mice, but dampened responses to norepinephrine and phenylephrine were observed by 10 and 15 weeks with Rho kinase influencing these effects in the 15-week-old animals. Despite these dampened vasoconstrictory responses, KO mice demonstrated increased mean arterial pressure from 8 weeks old. This hypertensive phenotype was associated with an increase in left ventricular weight, left ventricular systolic pressure, and diminished diastolic function. KO mice also show enhanced plasma norepinephrine turnover, suggesting an increased sympathetic outflow. In conclusion, our data suggest that global loss of arginase II activity results in hypertension. We suggest that this strain of mouse warrants further investigation as a potentially novel model of hypertension.
Huynh
Ngan N
NN
Vascular Pharmacology, Baker IDI Heart and Diabetes Institute, PO Box 6492 St Kilda Rd Central, Victoria, 8008 Australia.
Andrews
Karen L
KL
Head
Geoffrey A
GA
Khong
Sacha M L
SM
Mayorov
Dmitry N
DN
Murphy
Andrew J
AJ
Lambert
Gavin
G
Kiriazis
Helen
H
Xu
Qi
Q
Du
Xiao-Jun
XJ
Chin-Dusting
Jaye P F
JP
D000704:Analysis of Variance; D000818:Animals; D001119:Arginase / Q000378:metabolism* / Q000494:pharmacology; D001120:Arginine / Q000494:pharmacology*; D017704:Baroreflex; D001783:Blood Flow Velocity; D001795:Blood Pressure Determination; D002395:Catecholamines / Q000097:blood / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D006334:Heart Function Tests; D006973:Hypertension / Q000235:genetics* / Q000503:physiopathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009569:Nitric Oxide / Q000378:metabolism*; D010641:Phenotype; D011336:Probability; D011897:Random Allocation; D012680:Sensitivity and Specificity; D014508:Urea / Q000378:metabolism; D014655:Vascular Resistance / Q000235:genetics / Q000502:physiology; D014661:Vasoconstriction / Q000235:genetics / Q000502:physiology
D002395:Catecholamines; D009569:Nitric Oxide; D014508:Urea; D001120:Arginine; D001119:Arginase