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This Article Full Text Full Text (PDF) All Versions of this Article: 297/1/F163    most recent 00087.2009v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Hultström, M. Articles by Iversen, B. M. PubMed PubMed Citation Articles by Hultström, M. Articles by Iversen, B. M.

AT₁ receptor activation regulates the mRNA expression of CAT1, CAT2, arginase-1, and DDAH2 in preglomerular vessels from angiotensin II hypertensive rats

¹Renal Research Group, Institute of Medicine, Haukeland University Hospital, and ²Institute of Medicine, University of Bergen, Bergen, Norway

Submitted 21 February 2009 ; accepted in final form 15 April 2009

Previously, we found increased expression of L-arginine metabolizing enzymes in both kidneys from two-kidney, one-clip (2K1C) hypertensive rats (Helle F, Hultstrom M, Skogstrand T, Palm F, Iversen BM. Am J Physiol Renal Physiol 296: F78–F86, 2009). In the present study, we investigate whether AT₁ receptor activation can induce the changes observed in 2K1C. Four groups of rats were infused with 80 ng/min ANG II or saline for 14 days and/or given 60 mg·kg^–1·day^–1 losartan. Gene expression was studied in isolated preglomerular vessels by RT-PCR. Dose-responses to ANG II were studied in isolated preglomerular vessels with and without acute NOS inhibition [10^–4 mol/l N^G-nitro-L-arginine methyl ester (L-NAME)]. Expressions of endothelial nitric oxide synthase (eNOS), caveolin-1, and arginase-2 were not changed by ANG II infusion. CAT1 (0.3 8 ± 0.07 to 0.73 ± 0.12, P < 0.05), CAT2 (1.14 ± 0.29 to 2.74 ± 0.48), DDAH2 (1.09 ± 0.27 to 2.3 ± 0.46), and arginase-1 (1.08 ± 0.17 to 1.82 ± 0.22) were increased in ANG II-infused rats. This was prevented by losartan treatment, which reduced the expression of eNOS (0.97 ± 0.26 to 0.37 ± 0.11 in controls; 0.8 ± 0.16 to 0.36 ± 0.1 in ANG II-infused rats) and caveolin-1 (2.49 ± 0.59 to 0.82 ± 0.24 in controls and 2.59 ± 0.61 to 1.1 ± 0.25 in ANG II-infused rats). ANG II (10^–10 mol/l) caused vessels from ANG II-infused animals to contract to 53 ± 15% of baseline diameter and 90 ± 5% of baseline diameter in controls (P < 0.05) and was further enhanced by L-NAME to 4 ± 4% of baseline diameter (P < 0.05). In vivo losartan treatment reduced the reactivity of isolated vessels to 91 ± 2% of baseline in response to 10^–7 mol/l ANG II compared with 82 ± 3% in controls (P < 0.05) and prevented the increased responsiveness caused by ANG II infusion. In conclusion, CAT1, CAT2, DDAH2, and arginase-1 expression in renal resistance vessels is regulated through the AT₁ receptor. This finding may be of direct importance for NOS and the regulation of preglomerular vascular function.

caveolin-1; afferent arteriole; contraction; losartan