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

Abstract

Hultström M, Helle F, Iversen BM. AT1 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 297: F163-F168, 2009. First published April 22, 2009 doi:10.1152/ajprenal.00087.2009.-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 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 ⅐ kg Ϫ1 ⅐ day Ϫ1losartan. 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 [10Expressions of endothelial nitric oxide synthase (eNOS), caveolin-1, and arginase-2 were not changed by ANG II infusion. CAT1 (0.3 8 Ϯ 0.07 to 0.73 Ϯ 0.12, P Ͻ 0.05), CAT2 (1.14 Ϯ 0.29 to 2.74 Ϯ 0.48), DDAH2 (1.09 Ϯ 0.27 to 2.3 Ϯ 0.46), and arginase-1 (1.08 Ϯ 0.17 to 1.82 Ϯ 0.22) were increased in ANG II-infused rats. This was prevented by losartan treatment, which reduced the expression of eNOS (0.97 Ϯ 0.26 to 0.37 Ϯ 0.11 in controls; 0.8 Ϯ 0.16 to 0.36 Ϯ 0.1 in ANG II-infused rats) and caveolin-1 (2.49 Ϯ 0.59 to 0.82 Ϯ 0.24 in controls and 2.59 Ϯ 0.61 to 1.1 Ϯ 0.25 in ANG II-infused rats). ANG II (10 Ϫ10 mol/l) caused vessels from ANG II-infused animals to contract to 53 Ϯ 15% of baseline diameter and 90 Ϯ 5% of baseline diameter in controls (P Ͻ 0.05) and was further enhanced by L-NAME to 4 Ϯ 4% of baseline diameter (P Ͻ 0.05). In vivo losartan treatment reduced the reactivity of isolated vessels to 91 Ϯ 2% of baseline in response to 10 Ϫ7 mol/l ANG II compared with 82 Ϯ 3% in controls (P Ͻ 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.caveolin-1; afferent arteriole; contraction; losartan THE AFFERENT ARTERIOLES (AAs) are the main site for regulation of renal blood flow (RBF) and glomerular filtration rate (GFR). This control is mediated by three main mechanisms: first, hormonal factors (endocrine, autocrine or paracrine); second, the sympathetic nervous system; and third, the myogenic and tubuloglomerular feedback systems (11). ANG II is a key hormone in the regulation of RBF and GFR. However, its effect is in many situations balanced by vasodilators such as vasodilatory prostanoids and nitric oxide (NO) (6). Together these signaling substances are of major importance in the regulation of RBF in the normal kidney and probably more so in hypertensive models where the components of the reninangiotensi...

Nitric oxide in afferent arterioles after uninephrectomy depends on extracellularl-arginine

“…Contraction of isolated AA in response to ANG II stimulation was similar to what we previously have found in agar-infused vessels (11)(12)(13). Only AA from early UNX displayed increased contraction to ANG II after NOS inhibition, with a maximal response at ANG II of 10 Ϫ8 mol/l.…”

“…This is different from the effects of ANG II in 2K1C, in which the effect of L-NAME was detected at significantly higher ANG II concentrations (11). The fact that L-NAME does not increase the response to ANG II in controls is consistent with earlier experiments in agar-infused arterioles that do not have shear stress-induced NO release (11,13).…”

“…The increased NO release was associated with elevated expression of the cationic amino acid transporters 1 (CAT1) and 2 (CAT2) (11,13). One of the substrates of this transporter, L-arginine, is utilized by eNOS in the production of NO.…”

Renal neurohormonal regulation in heart failure decompensation

“…Combined inhibition of nitric oxide synthesis and ANG II stimulation uncovers a decreased contractility and almost no nitric oxide production in vessel preparations from animals with heart failure (26). This shows a marked difference from the effect of ANG II on afferent arterioles in high renin hypertension models (22,24) and during ANG II blockade in vivo (61). ANG II increases tubular sodium reabsorption (47), although reabsorption may be decreased by ANG II in the proximal nephron (37,64).…”

Cecropia pachystachya extract attenuated the renal lesion in 5/6 nephrectomized rats by reducing inflammation and renal arginase activity

“…and arginase 2 (ARG 2) is more abundant in the kidney (Schnorr et al, 2008). However, after the development of hypertension, increases the expression of ARG 1 and ARG 2 and L-arginine transporters in afferent arterioles are observed (Hultström et al, 2009). In inflammatory diseases, ARG 1 expression increases in macrophages (Schnorr et al, 2008).…”