Article

Variable renal atrial natriuretic factor gene expression in hypertension.

University of Ottawa Heart Institute, Ottawa, Ontario, Canada.
Hypertension (Impact Factor: 7.63). 07/1999; 33(6):1342-7. DOI: 10.1161/01.HYP.33.6.1342
Source: PubMed

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.

0 Followers
 · 
63 Views
  • Source
    [Show abstract] [Hide abstract]
    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 · 3.87 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: We investigated the antihypertensive effect of a methanol extract (ME) of fenugreek seeds and its methanol fraction (MF) in deoxycorticosterone acetate (DOCA)-salt-induced and fructose-induced hypertensive rats. In the DOCA model, DOCA (15 mg/kg, twice a week; s.c.) was administered in uni-nephrectomized animals for 4 weeks. Methanol extract of fenugreek seeds (30 mg kg−1 day−1; p.o.) and its methanol fraction (15 mg kg−1 day−1; p.o.) were evaluated for their antihypertensive effect. In the fructose model, drinking water was replaced with a 10% fructose solution for 6 weeks to induce hypertension. ME (100 mg kg−1 day−1; p.o.) was assessed for its antihypertensive effect in the fructose model. After completion of the treatment schedule, blood pressure and vascular reactivity to various agonists like serotonin (5-hydroxytryptamine; 5-HT), noradrenaline (NA), and adrenaline (Adr) were recorded in rats of both models. A dose-response curve (DRC) of 5-HT was carried out in isolated rat fundus strip of the fructose-induced hypertensive rats. Chronic administration of ME (30 mg kg−1 day−1; p.o.) and MF (15 mg kg−1 day−1; p.o.) of fenugreek seeds significantly reduced blood pressure in DOCA salt and ME (100 mg kg−1 day−1; p.o.) reduced blood pressure in fructose-induced hypertensive rats. Treatment with ME (100 mg kg−1 day−1; p.o.) in fructose model for 6 weeks shifted the DRC toward the right on rat fundus. Thus, fenugreek seeds exhibit a significant antihypertensive effect. The mechanism of action may partly involve the serotonergic antagonistic property involving the 5-HT2 receptor subtype.
    Pharmaceutical Biology 10/2008; 44(8):568-575. DOI:10.1080/13880200600896538 · 1.34 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Chromogranin A (CgA) is the major soluble protein co-stored and co-released with catecholamines (CAs) from secretory vesicles in the adrenal medulla chromaffin cells. Present in the diffuse neuroendocrine system, it has also been detected in rat and human cardiac secretory granules where it co-stores with natriuretic peptide hormones (NPs). Mounting evidence shows that CgA is a marker of cardiovascular dysfunctions (essential hypertension, hypertrophic and dilatative cardiomyopathy, heart failure) and precursor of the cardioactive peptides vasostatin-1 (VS-1) and catestatin (Cts). This review focuses on recent knowledge regarding the myocardial, coronary and anti-adrenergic actions of VS-1. In particular, the negative inotropism, lusitropism and coronary dilation effects of rat CgA1-64 (rCgA) and human recombinant STACgA1-78 (hrSTACgA1-78) are summarized with attention on their counteracting isoproterenol- and endothelin-1-induced positive inotropism, as well as ET-1-dependent coronary constriction. The interactions between vasostatins (VSs), NPs and CA receptors are proposed as a paradigm of the heart capacity to organize complex connection-integration processes for maintaining homeostasis under intense cardio-excitatory stimuli (myocardial stress).
    Regulatory Peptides 11/2010; 165(1):86-94. DOI:10.1016/j.regpep.2010.05.005 · 2.01 Impact Factor