1. [AT.sub.1] receptor activation regulates the mRNA expression of CAT1, CAT2, arginase-1, and DDAH2 in preglomerular vessels from angiotensin II hypertensive rats
- Author
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Hultstrom, Michael, Helle, Frank, and Iversen, Bjarne M.
- Subjects
Losartan -- Health aspects ,Angiotensin -- Properties ,Gene expression -- Observations ,Hypertension -- Diagnosis ,Kidneys -- Reports ,Messenger RNA ,Biological sciences - 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 A[T.sub.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 * [kg.sup.-1] * [day.sup.-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.sup.-4] mol/1 [N.sup.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 [+ or -] 0.07 to 0.73 [+ or -] 0.12, P < 0.05), CAT2 (1.14 [+ or -] 0.29 to 2.74 [+ or -] 0.48), DDAH2 (1.09 [+ or -] 0.27 to 2.3 [+ or -] 0.46), and arginase-1 (1.08 [+ or -] 0.17 to 1.82 [+ or -] 0.22) were increased in ANG II-infused rats. This was prevented by losartan treatment, which reduced the expression of eNOS (0.97 [+ or -] 0.26 to 0.37 [+ or -] 0.11 in controls; 0.8 [+ or -] 0.16 to 0.36 [+ or -] 0.1 in ANG II-infused rats) and caveolin-1 (2.49 [+ or -] 0.59 to 0.82 [+ or -] 0.24 in controls and 2.59 [+ or -] 0.61 to 1.1 [+ or -] 0.25 in ANG II-infused rats). ANG II ([10.sup.-10] mold) caused vessels from ANG II-infused animals to contract to 53 [+ or -] 15% of baseline diameter and 90 [+ or -] 5% of baseline diameter in controls (P < 0.05) and was further enhanced by L-NAME to 4 [+ or -] 4% of baseline diameter (P < 0.05). In vivo losartan treatment reduced the reactivity of isolated vessels to 91 [+ or -] 2% of baseline in response to [10.sup.-7] mol/l ANG II compared with 82 [+ or -] 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.sup.1] receptor. This finding may be of direct importance for NOS and the regulation of preglomerular vascular function. caveolin-1; afferent arteriole; contraction; losartan
- Published
- 2009