Cardiac hypertrophy in neonatal nephrectomized rats: the role of the sympathetic nervous system
- 204 Downloads
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 α1A-receptor protein expression, lower cardiac β1- and β2-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 α1A receptors), as well as increased α1A receptors and their agonist NE, might contribute to the observed hypertrophy.
KeywordsRemnant kidney Renalase Signaling
This work is supported by the Jeffress Foundation.
- 1.O’Regan S (1984) Cardiovascular abnormalities in paediatric patients with ESRD. In: Fine RN, Gruskin AB (eds) End-stage renal disease in children. Saunders, Philadelphia, pp 359–374Google Scholar
- 2.Scharer K, Ulmer HE (1985) Cardiovascular complications of renal failure. In: Holliday MA, Barratit TM, Vernier RL (eds) Pediatric nephrology (2nd edn). Williams and Wilkins, Baltimore, pp 887–896Google Scholar
- 3.Mitsnefes MM, Kimball TR, Kartal J, Witt SA, Glascock BJ, Khoury PR, Daniels SR (2006) Progression of left ventricular hypertrophy in children with early chronic kidney disease: 2-year follow-up study. J Pediatr 2149:671–675Google Scholar
- 4.Zoccali C, Mallamaci F, Parlongo S, Cutrupi S, Benedetto FA, Tripepi G, Bonanno G, Rapisarda F, Fatuzzo P, Seminara G, Cataliotti A, Stancanelli B, Malatino LS (2002) Plasma norepinephrine predicts survival and incident cardiovascular events in patients with end-stage renal disease. Circulation 105:1354–1359PubMedCrossRefGoogle Scholar
- 10.Garofolo MC, Seidler FJ, Auman JT, Slotkin TA (2002) Adrenergic modulation of muscarinic cholinergic receptor expression and function in the developing heart. Am J Physiol 282:R1356–R1363Google Scholar
- 12.Slotkin TA, Smith PG, Lau C, Bareis DL (1980) Functional aspects of development of catecholamine biosynthesis and release in the sympathetic nervous system. In: Parvez H, Parvez S (eds) Biogenic amines in development. Elsevier/North-Holland, Amsterdam, pp 29–48Google Scholar
- 36.Amann K, Rump LC, Simonaviciene A, Oberhauser V, Wessels S, Orth SR, Gross ML, Koch A, Bielenberg GW, Van Kats JP, Ehmke H, Mall G, Ritz E (2000) Effects of low dose sympathetic inhibition on glomerulosclerosis and albuminuria in subtotally nephrectomized rats. J Am Soc Nephrol 11:1469–1478PubMedGoogle Scholar
- 37.Goldstein DS (1988) Plasma catecholamines and essential hypertension: An analytical review. Hypertension 5:86–99Google Scholar
- 53.Akhter SA, Milano CA, Shotwell KF, Cho MC, Rockman HA, Lefkowitz RJ, Koch WJ (1997) Transgenic mice with cardiac overexpression of alpha1B-adrenergic receptors. In vivo alpha1-adrenergic receptor-mediated regulation of beta-adrenergic signaling. J Biol Chem 272:21253–21259PubMedCrossRefGoogle Scholar
- 59.Silberbach M, Gorenc T, Hershberger RE, Stork PJ, Steyger PS, Roberts CT (1999) Extracellular signal-regulated protein kinase activation is required for the anti-hypertrophic effect of atrial natriuretic factor in neonatal rat ventricular myocytes. J Biol Chem 274:24858–24864PubMedCrossRefGoogle Scholar