Effect of postnatal Leptin on cardiac structure and function.

Obesity in pregnancy is associated with cardiovascular dysfunction in adult offspring. We have previously reported an exaggerated leptin surge, in neonatal offspring of obese rats (1) associated with the development of sympathetic mediated hypertension and cardiac hypertrophy (2-3). We have now addressed the hypothesis that the high levels of leptin in early postnatal life may underlie early origin of hypertension and cardiac hypertrophy. To investigate the role of increased neonatal leptin exposure on the development of sympathetic mediated hypertension and the cardiac hypertrophy in offspring of obese dams. Pups from lean Sprague-Dawley rats were randomly assigned for intraperitoneal administration of recombinant rat leptin (LTx, 3mg/kg) or saline (S-Tx) at postnatal day 9-15. At day 23, juvenile rats were subjected to radiotelemetry surgery under general anaesthesia (2% isofluorane in O₂ at 2 l/ min) using a carotid artery placement of the small animal transmitters (DSIPhysioTel ® PA-C10). Pre and post-operative analgesia (Buprenorphine 0.1 mg/kg, intramuscular) was maintained for 24h. Heart rate and blood pressure were recorded after oneweek recovery by schedule sampling for 10 s every 5 min using A.R.T.10 software (Dataquest IV, DSI). Heart structure and function were analysed using in vivo micro-echocardiography (2% isofluorane, Vevo 770-ECHO system) and ex vivo langerdorf perfusion. The cardiomyocyte number and surface area were determined using hemomtoxylin-eosin and anti-laminin immunoflourescence. Neonatal leptin treated male and female rats (L-Tx) showed increased night-time (active period) systolic blood pressure (SBP [mmHg] mean±SEM: male L-Tx, 132±1 versus S-Tx, 119±1, n=6, p< 0.05; female L-Tx, 132±2 versus S-Tx, 119±1, n=6, p< 0.01, RM-ANOVA), in comparison to S-Tx. Female L-Tx demonstrated increased heart weight (P<0.05, n=6,t-test) with evidence of increased cardiomyocyte number at day 30. The in vivo imaging revealed altered left ventricle dimensions and diminished left ventricular systolic function and isolated heart showed evidence of impaired contractile function in the L-Tx versus S-Tx. This study implicates a central role for neonatal leptin in the origins of sympathetic mediated hypertension and cardiac morphology and function, in offspring of obese rodents. Evidence of cardiac dilatation together with impaired contractility may reflect early stages of heart failure. [ABSTRACT FROM AUTHOR]