Reduced endothelial nitric oxide synthase activation contributes to cardiovascular injury during chronic kidney disease progression
Por:
Amador-Martinez, Isabel, Perez-Villalva, Rosalba, Uribe, Norma, Cortes-Gonzalez, Cesar, Bobadilla, Norma A., Barrera-Chimal, Jonatan
Publicada:
1 ene 2019
Resumen:
Major cardiovascular events are a common complication in patients with chronic kidney disease (CKD). Endothelial dysfunction can contribute to the cardiovascular injury observed in CKD. Here, we used a rat model of acute kidney injury to CKD transition to investigate heart alterations in the pathway activating endothelial nitric oxide synthase (eNOS) and its impact on the cardiac injury observed during CKD progression. Fifty male Wistar rats were subjected to sham surgery (n = 25) or bilateral renal ischemia-reperfusion (IR-CKD) for 45 min (n = 25). Rats were studied on a monthly basis up to 5 mo (n = 5). In another set of sham and IR-CKD rats, l-arginine was administered starting on the third month after renal ischemia. CKD development and cardiac alterations were monitored in all groups. CKD was characterized by a progressive increase in proteinuria and renal dysfunction that was evident after the fifth month of followup. Heart hypertrophy was observed starting on the fourth month after ischemia-reperfusion. There was a significant increase in brain natriuretic peptide levels. In the heart, IR-CKD rats had increased eNOS phosphorylation at threonine 495 and reduced eNOS-heat shock protein-90a interactions. l-Arginine administration prevented the heart alterations observed during CKD and increased eNOS coupling/dimerization and activation. In summary, CKD progression is accompanied by cardiac hypertrophy, fibrosis, oxidative stress, and increased brain natriuretic peptide levels. These alterations were associated with limited eNOS activation in the heart, which may result in reduced nitric oxide bioavailability and contribute to cardiac injury during CKD.
Filiaciones:
Amador-Martinez, Isabel:
Laboratorio de Fisiología Cardiovascular y Trasplante Renal, Unidad de Medicina Translacional, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México and Instituto Nacional de Cardiología Ignacio Chávez, Mexico City, Mexico
Molecular Physiology Unit, Instituto de Investigaciones Biomedicas, Universidad Nacional Autonoma de Mexico, Mexico City, Mexico
Univ Nacl Autonoma Mexico, Inst Invest Biomed, Lab Fisiol Cardiovasc & Trasplante Renal, Unidad Med Translac, Mexico City, DF, Mexico
Inst Nacl Cardiol Ignacio Chavez, Juan Badiano 1,Sect 16 Belisario Dominguez, Mexico City 14080, DF, Mexico
Univ Nacl Autonoma Mexico, Inst Invest Biotned, Mol Physiol Unit, Mexico City, DF, Mexico
Perez-Villalva, Rosalba:
Molecular Physiology Unit, Instituto de Investigaciones Biomedicas, Universidad Nacional Autonoma de Mexico, Mexico City, Mexico
Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
Univ Nacl Autonoma Mexico, Inst Invest Biotned, Mol Physiol Unit, Mexico City, DF, Mexico
Inst Nacl Ciencias Med & Nutr Salvador Zubiran, Mexico City, DF, Mexico
Uribe, Norma:
Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
Inst Nacl Ciencias Med & Nutr Salvador Zubiran, Mexico City, DF, Mexico
Cortes-Gonzalez, Cesar:
Unidad de Investigación Biomédica en Cáncer, Instituto Nacional de Cancerología, Mexico City, Mexico
Inst Nacl Cancerol, Unidad Invest Biomed Canc, Mexico City, DF, Mexico
Bobadilla, Norma A.:
Molecular Physiology Unit, Instituto de Investigaciones Biomedicas, Universidad Nacional Autonoma de Mexico, Mexico City, Mexico
Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
Univ Nacl Autonoma Mexico, Inst Invest Biotned, Mol Physiol Unit, Mexico City, DF, Mexico
Inst Nacl Ciencias Med & Nutr Salvador Zubiran, Mexico City, DF, Mexico
Barrera-Chimal, Jonatan:
Laboratorio de Fisiología Cardiovascular y Trasplante Renal, Unidad de Medicina Translacional, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México and Instituto Nacional de Cardiología Ignacio Chávez, Mexico City, Mexico
Molecular Physiology Unit, Instituto de Investigaciones Biomedicas, Universidad Nacional Autonoma de Mexico, Mexico City, Mexico
Univ Nacl Autonoma Mexico, Inst Invest Biomed, Lab Fisiol Cardiovasc & Trasplante Renal, Unidad Med Translac, Mexico City, DF, Mexico
Inst Nacl Cardiol Ignacio Chavez, Juan Badiano 1,Sect 16 Belisario Dominguez, Mexico City 14080, DF, Mexico
Univ Nacl Autonoma Mexico, Inst Invest Biotned, Mol Physiol Unit, Mexico City, DF, Mexico
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