Variable renal atrial natriuretic factor gene expression in hypertension
ABSTRACT We have previously established the existence of atrial natriuretic factor (ANF) gene expression within the renal parenchyma. Neither the role nor the regulation of this extracardiac source of ANF is clearly defined. To determine whether renal ANF gene expression, similar to cardiac expression, is linked to the activity of the renin-angiotensin system (RAS), we compared renal ANF gene expression in rats after suprarenal aortic banding, a hypertension model associated with activation of RAS, and in the deoxycorticosterone acetate (DOCA)-salt model, which is characterized by depression of RAS. Renal ANF mRNA was measured with a quantitative competitive reverse transcription polymerase chain reaction method. DOCA-salt hypertension significantly reduced the expression of renal ANF. In contrast, aortic banding significantly increased renal ANF expression. In both cases, ANF gene expression in the heart increased. Ramipril treatment at 10 micrograms/kg of aortic-banded rats, a treatment that specifically affects local RAS but maintains hypertension, normalized renal ANF mRNA levels. Altogether, these results suggest that renal ANF gene expression is modulated by local RAS and is independent of circulating RAS and hypertension per se. The marked decrease of renal ANF mRNA in DOCA-salt hypertension suggests a pathogenic role for renal ANF gene downregulation by decreasing the sodium excretory mechanism mediated by the local expression of ANF acting on receptors found in the inner medullary collecting ducts. In aortic banding, renal ANF gene expression upregulation suggests a local compensatory function consistent with the consensus role of natriuretic peptides in the modulation of RAS, thus ameliorating the sodium-retaining effects of renal underperfusion.
- SourceAvailable from: Chao-Sheng Lo
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- "However, up-regulation of ANP mRNA expression has been demonstrated in extra-atrial tissues such as the kidneys (Shin et al., 1997, 1998; Totsune et al., 1998; Ogawa et al., 1999; Obineche et al., 2006; Bae et al., 2007), adrenal glands (Lai et al., 2000), and cardiac ventricles (Shin et al., 1998). In the kidneys, in several disorders including diabetes (Shin et al., 1997; Obineche et al., 2006), water deprivation (Shin et al., 1998), unilateral ureteral obstruction (Bae et al., 2007), suprarenal aortic banding (Ogawa et al., 1999), and remnant kidneys of rats with reduced renal mass (Totsune et al., 1998), ANP synthesis has been found to increase markedly; however, the exact pathophysiological significance of kidney-synthesized ANP has not yet been defined. Cardiac atrium-synthesized ANP plays an important role in the regulation of extracellular fluid volume homeostasis (de Bold et al., 1981; Brenner et al., 1990). "
ABSTRACT: Up-regulation of atrial natriuretic peptide (ANP) mRNA in the kidneys in several disorders has been demonstrated; however, evidence that ANP synthesized by the kidney exerts a local function has never been produced. Therefore, we investigated whether endogenous ANP could modulate high glucose-stimulated TGF-beta1, collagen type I and nuclear factor-kappaB (NF-kappaB) in NRK-52E cells using transfection of ANP and ANP small interfering RNA (siANP). NRK-52E cells were grown with or without transfection with ANP plasmid; cells were also transfected with ANP siRNA or control siRNA. These cells were then stimulated with a high glucose concentration to modulate ANP, TGF-beta1, collagen type I, NF-kappaB and IkappaB-alpha, and the results showed that ANP, TGF-beta1, collagen type I and NF-kappaB significantly increased in untransfected cells, and the transfection of ANP significantly attenuated high glucose-activated TGF-beta1, collagen I and NF-kappaB expression. ANP siRNA knocked-down ANP but significantly increased TGF-beta1 and collagen I under normal glucose conditions; ANP siRNA decreased IkappaB-alpha but strongly enhanced high glucose-activated TGF-beta1, collagen type I and NF-kappaB. In contrast, medium from ANP-transfected cells attenuated high glucose-activated TGF-beta1 and collagen type I expression in NRK-52E cells transfected with siANP. In conclusion, our results demonstrated that siANP increased activation of TGF-beta1, collagen type I and NF-kappaB in NRK-52E cells under high glucose conditions, and medium from ANP-transfected cells attenuated high glucose-activated TGF-beta1 and collagen type I. This is the first study to demonstrate the auto/paracrine action of endogenous ANP in renal tubular cells on the attenuation of hyperglycemia-activated TGF-beta1 and NF-kappaB expression. J. Cell. Physiol. 219: 776-786, 2009. (c) 2009 Wiley-Liss, Inc.Journal of Cellular Physiology 06/2009; 219(3):776-86. DOI:10.1002/jcp.21728 · 3.84 Impact Factor
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- "In intact kidney, we previously reported that renal ANP mRNA expression was upregulated in deoxycorticosterone acetate (DOCA)-salt-treated rats (Lee et al. 1996). Increased renal ANP mRNA expression has also been shown in remnant kidney of rats with reduced renal mass (Totsune et al. 1998), in rats with suprarenal aortic banding (Ogawa et al. 1999), and in rats with water deprivation and salt restriction (Shin et al. 1998). In the present study, we further showed that the ANP mRNA signal and ANP-like immunoreactive staining, as assessed by in situ hybridization and immunohistochemical study, respectively, were strongly increased in PST and medullary CD of diabetic rats compared to those in normal rats. "
ABSTRACT: Increased intrarenal atrial natriuretic peptide (ANP) mRNA expression has been reported in several disorders. To further investigate the action of renal ANP, we need to elucidate the exact site of its alteration in diseased kidneys. ANP mRNA and ANP were detected by in situ hybridization and immunohistochemistry in the kidneys from five normal and five diabetic rats. Renal ANP mRNA in eight normal and nine diabetic rats was measured by RT-PCR with Southern blot hybridization. In normal and diabetic rats, the distribution of ANP mRNA and ANP-like peptide was mainly located in proximal, distal, and collecting tubules. However, diabetic rats had significant enhancement of ANP mRNA and ANP-immunoreactive staining in the proximal straight tubules, medullary thick ascending limbs, and medullary collecting ducts. ANP mRNA in the outer and inner medulla of nine diabetic rats increased 5.5-fold and 3.5-fold, but only 1.8-fold in the renal cortex. This preliminary study showed that ANP mRNA and ANP immunoreactivity in proximal straight tubules, medullary thick ascending limb, and medullary collecting ducts apparently increased in diabetic kidneys. These findings imply that ANP synthesis in these nephrons may involve in adaptations of renal function in diabetes.Journal of Histochemistry and Cytochemistry 12/2002; 50(11):1501-8. DOI:10.1177/002215540205001110 · 1.96 Impact Factor
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- "Since nitric oxide (NO) inhibits Na þ uptake, increased NO formation has been postulated to be one mechanism for saltadaptation . Increased expression of atrial natriuretic peptide (ANF) gene has been linked to activation of the renin–angiotensin–aldosterone pathway in rats after suprarenal aortic banding . This suggests that the systematic evaluation of the effect of dietary salt on gene expression may lead to identification of genes important in salt-adaptation and hypertension. "
ABSTRACT: Aquaporin-2 (AQP-2) is a vasopressin-regulated water channel in the kidney collecting duct. AQP-2 transcript has been identified by transcriptional profiling of rat kidneys as being regulated by dietary salt. We compared renal AQP-2 transcript expression in Sprague-Dawley and Dahl salt-sensitive (SS/Jr) rats using real-time RT-PCR. Expression of AQP-2 transcript is 5-fold less (P<0.01) in the Sprague-Dawley and 3-fold greater in Dahl SS/Jr rats (P<0.01) on high versus basal NaCl diets. The AQP-2 coded sequence was identical in Sprague-Dawley and Dahl SS/Jr rats. The present results provide evidence that: (1)AQP-2 plays a role in salt adaptation and (2) regulation of aquaporin transcript expression by salt is altered in the Dahl SS/Jr rat.Biochemical and Biophysical Research Communications 08/2002; 296(3):755-8. DOI:10.1016/S0006-291X(02)00896-3 · 2.30 Impact Factor