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

Am J Physiol Renal Physiol. 2009 Jul;297(1):F163-8. doi: 10.1152/ajprenal.00087.2009. Epub 2009 Apr 22.

Abstract

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 AT(1) 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 x kg(-1) x 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 AT(1) receptor. This finding may be of direct importance for NOS and the regulation of preglomerular vascular function.

MeSH terms

  • Amidohydrolases / genetics
  • Amidohydrolases / metabolism*
  • Angiotensin II / pharmacology
  • Angiotensin II Type 1 Receptor Blockers / pharmacology
  • Animals
  • Arginase / genetics
  • Arginase / metabolism*
  • Arterioles / metabolism*
  • Arterioles / pathology
  • Calcium Channels / genetics
  • Calcium Channels / metabolism*
  • Disease Models, Animal
  • Hypertension / metabolism*
  • Hypertension / pathology
  • Kidney Glomerulus / blood supply*
  • Losartan / pharmacology
  • Nitric Oxide / metabolism
  • Nitric Oxide Synthase Type III / metabolism
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Wistar
  • Receptor, Angiotensin, Type 1 / drug effects
  • Receptor, Angiotensin, Type 1 / metabolism*
  • TRPV Cation Channels / genetics
  • TRPV Cation Channels / metabolism*

Substances

  • Angiotensin II Type 1 Receptor Blockers
  • Calcium Channels
  • RNA, Messenger
  • Receptor, Angiotensin, Type 1
  • TRPV Cation Channels
  • TRPV5 protein, rat
  • TRPV6 channel
  • Angiotensin II
  • Nitric Oxide
  • Nitric Oxide Synthase Type III
  • Amidohydrolases
  • Arginase
  • dimethylargininase
  • Losartan