Oral subacute treatment with nebivolol completely prevents cardiac postischemic stunning in rats, but hyperthyroidism reduces this protection: mechanisms involved.

RAGONE MI; BAYLEY M; LOPEZ S; DIAZ, RG; CONSOLINI AE

NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY

SPRINGER

Lugar: Berlin; Año: 2023

0028-1298

Nebivolol could prevent dysfunction in patients suffering myocardial ischemia. However, influence of hyperthyroidism is not known. Consequences and mechanisms of nebivolol treatment were investigated in isolated hearts from euthyroid (EuT) and hyperthyroid (HpT) rats. Rats were orally treated during 1 week with 20 mg/kg/day nebivolol (O-Neb), 30 mg/kg/day atenolol (O-Ate), or not treated (C). Isolated perfused hearts were exposed to global ischemia and reperfusion (I/R)inside a flow calorimeter. Left diastolic ventricular pressure, developed contractile pressure (P), and total heat rate (Ht) were continuously measured, while infarct size was measured after 2-h R. EuT-C and HpT-C hearts developed similarly low postischemic contractile recovery and economy (P/Ht). Nebivolol totally prevented dysfunction and reduced infarction size in EuT hearts, but partially improved recovery in HpT rat hearts. Contrarily, oral atenolol totally prevented dysfunction in HpThearts but partially in EuT hearts. Nebivolol effects were reversed by perfusing L-NAME in both conditions, but partially reduced by aminoguanidine in HpT. However, L-NAME increased P and P/Ht recoveries in EuT-C and HpT-C rat hearts, as well as melatonin. Oral nebivolol prevented post-ischemic dysfunction and infarction in EuT hearts due to adrenergic β1 blockade and activation of iNOS and/or eNOS, but the effect was attenuated in HpT hearts by excessive iNOS-dependentnitrosative pathways.