Angiotensin II type 1 receptor: role in renal growth and gene expression during normal development

Abstract

To determine whether angiotensin II (ANG II) modulates renal growth and renin and angiotensin type 1 (AT1) gene expression via AT1 during development, weanling rats were given ANG II antagonist losartan (DuP 753) for 3 wk. Body weight (g), kidney weight (g), and kidney weight-to-body weight ratio were lower in losartan-treated rats (162 +/- 7, 1.6 +/- 0.06, and 9.5 +/- 0.1 x 10(-3)) than in control rats (184 +/- 5, 1.8 +/- 0.07, and 10.1 +/- 0.1 x 10(-3); P < 0.05). Renal DNA content (mg/kidney) was lower in losartan-treated (2.4 +/- 0.17) than in control rats (3.3 +/- 0.31; P < 0.05), whereas protein-to-DNA and RNA-to-DNA ratios were similar in losartan-treated and control rats. Renin mRNA levels were sevenfold higher in losartan-treated than in control rats, as determined by quantitative standardized dot blot analysis. In addition, blockade of AT1 with losartan induced recruitment of renin-synthesizing and renin-containing cells in the renal vasculature, as determined by immunocytochemistry and in situ hybridization. To establish whether AT1 blockade has a direct effect on renin gene expression, freshly isolated renin-producing cells were exposed in vitro to losartan (10(-6) M) or culture media (control). Losartan induced a twofold increase in steady-state renin mRNA levels above control (P < 0.05). Intrarenal AT1 mRNA levels were not altered by losartan given either in vivo or in vitro to freshly dispersed cells. To define whether immature renin-secreting cells are responsive to ANG II, renin release was determined by reverse hemolytic plaque assay.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin Subtype-2 Receptors Inhibit Renin Biosynthesis and Angiotensin II Formation

“…33 Previously published data demonstrated a short negative feedback loop of the AT 1 receptor to suppress renin and Ang II production. 1,18,19 A regulatory role for the AT 2 receptor in modulating RAS activity has not been described previously. A murine strain with disruption of the AT 2 receptor gene displays slightly elevated baseline blood pressure, exaggerated vasopressor response to Ang II, increased prostaglandin E2 (PGE2), and reduced NO and cGMP production.…”

“…The AT 2 receptor is expressed abundantly during fetal development and declines after birth. [1][2][3] In mammalian adults, the AT 2 receptor had been reported in multiple organs, including the kidney. 4 -6 Currently, the AT 2 receptor has several described functions related to inhibition of cell growth, promotion of cell differentiation, and stimulation of apoptosis.…”

“…Most of the known physiological functions and pathologic effects associated with Ang II are mediated by the angiotensin subtype 1 (AT 1 ) receptor, including renin inhibition. 1 In contrast, the functions of the angiotensin subtype 2 (AT 2 ) receptor are still being elucidated. The AT 2 receptor is expressed abundantly during fetal development and declines after birth.…”

New insights into the renoprotective actions of the renin inhibitor aliskiren in experimental renal disease

“…It seems doubtful that all of the labeled aliskiren observed in glomeruli in these studies was bound to renin: it is highly unlikely that so much renin was present in the glomeruli of the normotensive rats used in this study. 69,95,96 Moreover, it seems similarly implausible that exposure to aliskiren for 2 h in normotensive rats could have induced recruitment of such high levels of glomerular renin, as has been shown in pre-glomerular vessels after chronic RAAS blockade, 97 especially as aliskiren is a relatively weak inhibitor of rat renin (Table 1). However, some of the label seen in glomeruli may have reflected aliskiren bound to renin that possibly was present in the mesangial matrix.…”

Expressing urine from a gel disposable diaper for biomonitoring using phthalates as an example

“…The AT 2 receptors are primarily located in the undifferentiated mesochyme within the nephrogenic zone. Blockade of this system either pharmacologically or by using gene knockouts leads to extensive renal vascular abnormalities (Tufro-McReddie et al, 1994). Nephrogenesis is complete prior to birth in the human, although substantial growth and maturation of function still occur postnatally.…”