Actividades del Laboratorio

Atorvastatina previene el aumento de TA en IRC

ATORVASTATIN PREVENTS SALT-INDUCED INCREASES IN BLOOD PRESSURE (BP) BUT NOT PROTEINURIA IN RATS WITH 5/6 NEPHRECTOMY-INDUCED CHRONIC RENAL INSUFFICIENCY (CRI).

Luis I Juncos, Luis A Juncos, Fernando L Martín, Sandra T Baigorria, María E Pasqualini, Maria C Fiore, Aldo Eynard, Néstor H García. J. Robert Cade Foundation-CONICET, Cordoba, Argentina and Mayo Clinic, Rochester, MN,

Background: CRI is characterized by progressive renal injury accompanied by the development of salt-sensitive hypertension. The mechanisms for the unrelenting renal injury and salt-sensitivity include increases in BP, oxidant stress and inflammation, as well as altered synthesis and removal of nitric oxide (NO); all of which are worsened by a high salt diet (HSD). Because HMG-CoA inhibitors have beneficial effects on oxidant stress, inflammation and NO metabolism, they may be useful during CRI. However, there is limited information on their effects in CRI, particularly in the setting of HSD.

Objective: To determine whether atorvastatin prevents salt-induced increases in BP and progression of renal injury in rats with the CRI.

Methods: Male Sprague Dawley rats were subjected to either 5/6 nephrectomy (Nx) or sham surgery. Two weeks later, they were placed into metabolic cages and randomized in 4 groups: 1) normal NaCl diet, 2) normal NaCl diet+atorvastatin (50mg/kg/day), 3) HSD, and 4) HSD+atorvastatin. We monitored, systolic BP (by tail cuff plethysmography), mean BP (via arterial cannula), renal function and injury (via serum creatinine, proteinuria), sodium balance, oxidative stress (as measured by renal excretion of HHT [12(S)-hydroxy 5,8,10 (Z,E,E)-heptadecatrienoic acid]), and NO status (via renal excretion of nitrites and renal cortical expression of eNOS).

Results: The Nx rats maintained on a normal NaCl diet did not have a higher BP than the sham rats but had already developed proteinuria. Atorvastatin did not alter BP but prevented the rise of proteinuria in these rats (from 25.8±4.1 to 30.5±7.2 mg/24 hr). This beneficial effect was associated with an increase in the NO parameters (urinary nitrites and renal eNOS) and a decrease in oxidative stress (urinary HHT). The HSD increased the mean BP of Nx rats (from 124.9±4.3 to 135.3±3.4 mmHg; p < 0.01) but not of the sham rats (from 111.3±2.5 to 116.2±1.1 mmHg). This hypertensive response was associated with salt retention and worsening proteinuria (84.7±8.3 mg/24 hr). Atorvastatin prevented the elevation in BP (121.2±4.3 vs. 121.9±3.3 mmHg) blunted the positive sodium balance (primarily via enhanced renal sodium excretion). However, despite these beneficial effects, atorvastatin did not prevent Nx+HSD-induced proteinuria, nor did it restore the balance between NO and oxidative stress.

Escrito por fjrc el 07/10/2007 16:23 | Comentarios (0)

Atorvastatina previene el dano renal

ATORVASTATINA PREVIENE EL DAÑO RENAL INDUCIDO POR LA DIETA ALTA EN SODIO EN RATAS NORMOTENSAS.

La ingesta alta de sodio es un factor de riesgo de daño renal. Estos efectos nocivos de la sobrecarga salina se atribuyen a su capacidad de aumentar la tensión arterial (TA). Sin embargo, el daño renal podría resultar del aumento del estrés oxidativo Independientemente de los niveles de TA. Mientras la dieta alta en sodio (DANa) induce en ratas Wistar normotensas hipertrofia miocárdica, sus efectos directos sobre el riñón no han sido definidos. Por otra parte, las estatinas han demostrado reducir la proteinuria y poseer propiedades anti-inflamatorias independientes de sus efectos sobre la colesterolemia. Por ello, nuestro objetivo fue demostrar que la DANa en ratas normotensas induce hiperfiltración y esclerosis glomerular y que ambas pueden ser prevenidas por la Atorvastatina. Métodos: Ratas Wistar macho fueron estudiadas durante 45 días divididas en 4 grupos: Control, Atorvastatina (Atorv) (50mg/kg.día), DANa (4% ClNa) y DANa+Atorv. Se evaluó la TA, proteinuria de 24 hs, balance de sodio, filtrado glomerular, volumen glomerular (VG) e histología renal. Resultados: La Proteinuria al día 45 en el Control fue 4.5±2.0 mg/24hs. La DANa la aumentó de 4.4±1.5 mg/24hs a 20.8±2.3 mg/24hs (p<0.05) durante el período experimental, sin observarse cambios en la TA. Atorvastatina previno el aumento de la proteinuria. El VG al día 45 fue en el Control 3.33*106±0.26 μm3, la DANa lo incrementó a 4.40*106±0.58 μm3 (p<0.05) y desarrolló esclerosis glomerular y adherencias glomerulares capsulares leves. Todos estos cambios se previnieron por Atorvastatina (VG: 3.64*106±0.47 μm3, p<0.05 vs DANa). Conclusiones: La DANa aumenta el volumen glomerular, la proteinuria y causa esclerosis glomerular. La Atorvastatina previno el daño glomerular inducido por la DANa, posiblemente mediante mecanismos anti-inflamatorios, independientes de la colesterolemia y de la tensión arterial.

Escrito por fjrc el 07/10/2007 16:19 | Comentarios (0)

Renal protection in radiation-induced nephritis

RENAL PROTECTION IN RADIATION-INDUCED NEPHRITIS

Juncos LI,  Baigorria S, García NH, Martín F, Juncos LA. IPEM Cordoba, Argentina and Mayo Clinic, Rochester Minnesota

En Espera

Escrito por fjrc el 07/10/2007 16:16 | Comentarios (0)

Efecto de la puromicina en la funcion renal

Angiotensin II-Independent Abnormal Renal Vascular Reactivity During Puromycin Nephropathy

Isoprostanes stimulate chloride transport (JCl) and prevent nitric oxide-induced inhi

Isoprostanes stimulate chloride transport (JCl) and prevent nitric oxide-induced inhibition of JCl in the cortical thick ascending limb (cTAL) via a protein kinase A-dependent mechanism.

Nestor H Garcia, MD, PhD, Pablo D Cabral, MD, Luis A Juncos, MD and Luis I Juncos, MD. Renal Physiology, J Robert Cade Foundation, Cordoba, Cordoba, Argentina; Renal Physiology, J Robert Cade Foundation CONICET, Cordoba, Cordoba, Argentina and Mayo Clinic, Rochester, MN, United States.

Superoxide (O2-) is thought to play an important role in the pathophysiology of salt-sensitive hypertension. One of its primary targets is the cTAL, where it increases NaCl reabsorption via its direct actions, or by quenching nitric oxide (NO; an inhibitor of NaCl reabsorption). However, the binding of O2- to NO results in the formation of isoprostanes, which possess biological activity and thus may also contribute to O2- effects on the cTAL. Therefore, we tested whether 8-iso-prostaglandin F2 (8-iso-PGF2; the major isoprostane isoform) increases basal JCl and/or prevents NO-induced decreases in JCl, in isolated microperfused rabbit cTAL. Basal JCl was 274±85 pmol/min/mm and remained stable in time control experiments, whereas addition of 10-6 M of sodium nitroprusside (SNP; an NO donor) or 10-4 M furosemide (a direct blocker of the NKCC2 cotransporter) decreased JCl by 44% and 88%, respectively. Addition of 10-4M 8-iso-PGF2 to the lumen increased basal JCl by 53% (315±46 pmol/min/mm; p<0.01), and reversed the inhibitory effect of SNP, but not furosemide, suggesting that isoprostanes can promote an increase in NaCl reabsorption in the cTAL. We next evaluated the role of cAMP-dependent protein kinase A in mediating isoprostane-induced NaCl reabsorption. We first examined whether isoprostanes increase cAMP levels in the cTAL; 8-iso-PGF2 increased intracellular cAMP (from 18±1 to 35±1 fmol/min/mm; p<0.05). Finally, we tested whether H89, a protein kinase A inhibitor, blocks the effects of isoprostanes on JCl in the cTAL. H89 decreased basal JCl (from 280± 22 a 216±16; p< 0.001) and blocked 8-iso-PGF2-induced increases in JCl (216±16 vs. 209±23). We conclude that 8-iso-PGF2 causes activation of cAMP-dependent protein kinase A, which in turn increases basal JCl and prevents NO-induced inhibition of JCl in the cTAL. These effects may contribute to oxidant-induced salt retention and hypertension.

Escrito por fjrc el 07/10/2007 15:52 | Comentarios (0)

Nuestros Proyectos de Coenzima Q10

En preparacion

Escrito por fjrc el 07/10/2007 15:48 | Comentarios (1)

Pizza Time

Escrito por fjrc el 07/10/2007 15:44 | Comentarios (1)