Submitted on February 13, 2009
Revised on April 15, 2009
Accepted on April 15, 2009
AT1 receptor activation regulates the mRNA expression of CAT-1, CAT-2, Arginase-1 and DDAH-2 in preglomerular vessels from angiotensin II hypertensive rats
Michael Hultström1*, Frank Helle1, and Bjarne Magnus Iversen2
1 University of Bergen
2 Institute of Medicine, University of Bergen
* To whom correspondence should be addressed. E-mail: michael.hultstrom{at}med.uib.no.
Previously we found increased expression of L-arginine metabolising enzymes in both kidneys from two-kidney, one-clip (2K1C) hypertensive rats. In the present study we investigate if 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/day Losartan. Gene expression was studied in isolated preglomerular vessels by RTPCR. Dose-responses to ANG II were studied in isolated preglomerular vessels with and without acute NOS inhibition (10-4 mol/L L-NAME). Expressions of eNOS, caveolin-1 and Arginase-2 were not changed by ANG II infusion. CAT-1 (0.38±0.07 to 0.73±0.12, P<0.05), CAT-2 (1.14±0.29 to 2.74±0.48), DDAH-2 (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). 10-10 mol/L ANG II 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 ANGII compared to 82±3% in controls (P<0.05) and prevented the increased responsiveness caused by ANGII infusion. In conclusion, CAT-1, CAT-2, DDAH-2 and Arginase-1 expressions in renal resistance vessels are regulated through the AT1 receptor. This finding may be of direct importance for nitric oxide synthesis and the regulation preglomerular vascular function.
