Beta-adrenergic blockade via atenolol negatively affects body and heart mass and renal morphology in the developing chicken (Gallus Gallus Domesticus).

Abstract

Atenolol is a widely prescribed β₁-cardioselective blocker. We studied atenolol effects on cardiac and renal development in day 18 (D18) chicken embryos. Embryos were dosed with atenolol (3 μg atenolol/g estimated embryo mass) for three days during one of the mesonephric kidney stage (D7-D9), mesonephric-metanephric stage (D11-D13), or metanephric stage (D15-D17), and then sampled on D18. Wet embryo body mass in atenolol-treated groups was reduced at D18 (P < 0.01). Wet heart mass of atenolol-treated embryos was significantly (P < 0.01) reduced in the mesonephric stage on D18. Similarly, kidney mass in atenolol-treated mesonephric and metanephric stages was significantly reduced at D18. Nephron density was 40 % lower following atenolol treatment during the mesonephros stage. Individual glomerular areas of mesonephric- and metanephric-treated stages were significantly larger (P < 0.01) than controls, but overall glomerular area was reduced in the meso- and meso-metanephros populations. Collectively, these data suggest that chronic atenolol treatment results in major renal remodeling and that the mesonephros renal stage (D7-D9), is the critical window for effects of atenolol on renal morphology. Acute atenolol application at D11 through D19 had no effect on mean arterial blood pressure or heart rate, even though these variables were acutely altered as early as Day 15 by isoproterenol. Collectively, these data suggest that the morphological effects of atenolol were not the result of altered perfusion. Further experiments are required to determine if reduced embryo, cardiac and renal masses are specific to chronic atenolol treatment, or whether other β blockers might have similar effects.