1. Arginase II knockout mouse displays a hypertensive phenotype despite a decreased vasoconstrictory profile.
- Author
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Huynh NN, Andrews KL, Head GA, Khong SM, Mayorov DN, Murphy AJ, Lambert G, Kiriazis H, Xu Q, Du XJ, and Chin-Dusting JP
- Subjects
- Analysis of Variance, Animals, Arginase pharmacology, Baroreflex, Blood Flow Velocity, Blood Pressure Determination, Catecholamines blood, Catecholamines metabolism, Disease Models, Animal, Female, Heart Function Tests, Male, Mice, Mice, Inbred C57BL, Mice, Knockout, Phenotype, Probability, Random Allocation, Sensitivity and Specificity, Urea metabolism, Vascular Resistance genetics, Vascular Resistance physiology, Vasoconstriction genetics, Vasoconstriction physiology, Arginase metabolism, Arginine pharmacology, Hypertension genetics, Hypertension physiopathology, Nitric Oxide metabolism
- Abstract
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.
- Published
- 2009
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