Upregulation of Arginase Expression and Activity in Hypertensive Rats Exposed to Chronic Intermittent Hypobaric Hypoxia

Abstract

The aim of this study was to analyze the activity and expression levels of arginase I and II and to monitor the cardiovascular and hematological responses in tolerant and intolerant rats exposed to chronic intermittent hypobaric hypoxia (CIHH). Male Wistar rats (age: 3.0 +/- 0.4 months, weight: 250 +/- 25 g; n = 30) were randomly divided into two groups: CIHH2 x 2 (2 days hypoxia, 2 days normoxia, n = 20) and NX (normoxia, n = 10). The hypoxia was simulated in a hypobaric chamber at 428 torr. Tolerance was determined according to a previous protocol. Arginase activity was measured in lung and heart tissues, and the expression levels were determined by a (RT-PCR) assay in lung tissue. Results showed that the intolerants rats had lower body weight, higher hematocrit (Hct) (74 +/- 4% vs. 61 +/- 2%, p < 0.05), higher values of systolic blood pressure (SBP) (183 +/- 3.7 mmHg vs. 147 +/- 5.4 mmHg, p < 0.05), and higher arginase activity. In addition, RT-PCR analysis from lung tissue showed an overexpression of arginase II in the intolerant group (p < 0.01). However, tolerants had similar values as the NX group (p = ns). Further, a correlation was found between arginase activity and SBP in the heart (r(2) = 0.596, p < 0.001). An upregulation of arginase type II could be pivotal in understanding the pathogenesis of systolic hypertension and probably other phenomena associated with intermittent hypobaric hypoxia. A schematic explanation of these relations is proposed.