Cardiac hypertrophy in neonatal nephrectomized rats: the role of the sympathetic nervous system.
Cardiac hypertrophy is frequently encountered in patients with renal failure and represents an independent risk factor for cardiovascular morbidity and mortality. The pathogenesis of cardiac hypertrophy is related to multiple factors, including excess adrenergic activity. This study investigated how renal injury in the early stages of life affects the adrenergic system and thereby potentially influences cardiac growth. Biomarkers of cardiac hypertrophy were used to assess adrenergic function. Newborn male Sprague-Dawley rats were allocated to three groups of five rats each: 5/6 nephrectomy (Nx), pair-fed controls (PF), and sham-operated (SH). Nx animals had significantly higher plasma urea nitrogen, serum creatinine, and mean arterial blood pressure. The heart-weight/body-weight ratio of the Nx cohort was higher than SH and PF (p < 0.001) groups. Plasma norepinephrine (NE) of Nx animals was almost twofold higher than SH and PF (p < 0.01) animals. Compared with SH and PF, Nx animals had higher alpha1A-receptor protein expression, lower cardiac beta1- and beta2-receptor protein expression (p < 0.05), but higher G-protein-coupled receptor kinase-2 (GRK2) expression (p < 0.05). Norepinephrine transporter protein (NET) and renalase protein expression in cardiac tissue from Nx pups were significantly lower than SH and PF. Our data suggest that early age Nx animals have increased circulating catecholamines due to decreased NE metabolism. Enhancement of cardiac GRK2 and NE can contribute to cardiac hypertrophy seen in Nx animals. Furthermore, AKT (activated via alpha1A receptors), as well as increased alpha1A receptors and their agonist NE, might contribute to the observed hypertrophy.
Ghosh
Siddhartha S
SS
Division of Nephrology, VCU Medical Center, Virginia Commonwealth University, MCV Station, Box 980160, Richmond, VA, 23298-0160, USA. ssghosh@hsc.vcu.edu
Krieg
Richard J
RJ
Sica
Domenic A
DA
Wang
Ruipeng
R
Fakhry
Itaf
I
Gehr
Todd
T
D000818:Animals; D000831:Animals, Newborn; D015415:Biomarkers / Q000378:metabolism; D001794:Blood Pressure; D006332:Cardiomegaly / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005260:Female; D054769:G-Protein-Coupled Receptor Kinase 2 / Q000378:metabolism; D006977:Hypertension, Renal / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D009392:Nephrectomy; D050484:Norepinephrine Plasma Membrane Transport Proteins / Q000378:metabolism; D009929:Organ Size; D011247:Pregnancy; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011942:Receptors, Adrenergic, alpha / Q000378:metabolism; D011943:Receptors, Adrenergic, beta / Q000378:metabolism; D051437:Renal Insufficiency / Q000378:metabolism* / Q000503:physiopathology*; D015398:Signal Transduction / Q000502:physiology; D013564:Sympathetic Nervous System / Q000502:physiology*
D015415:Biomarkers; D050484:Norepinephrine Plasma Membrane Transport Proteins; D011942:Receptors, Adrenergic, alpha; D011943:Receptors, Adrenergic, beta; C493226:Slc6a2 protein, rat; D051057:Proto-Oncogene Proteins c-akt; C496569:Grk2 protein, rat; D054769:G-Protein-Coupled Receptor Kinase 2; D048049:Extracellular Signal-Regulated MAP Kinases
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