Cardiology Letters 2014, 23(6):390-396

The effect of ivabradine administration on heart rate, blood pressure, and secretion of epinephrine, norepinephrine, and corticosterone during stress response in rats

Hegedušová N¹, Ondičová K^{1, 2}, Miková L^{1, 2}, Lejavová K^{1, 2}, Horváthová L², Tillinger A², Mravec B^{2, 3}

¹ Ústav patologickej fyziológie, Lekárska fakulta Univerzita Komenského v Bratislave

² Ústav experimentálnej endokrinológie, SAV v Bratislave

³ Fyziologický ústav, Lekárska fakulta Univerzita Komenského v Bratislave, Slovenská republika

Aim: The extent and duration of neuroendocrine stress response is regulated also by afferent signals from visceral organs. The aim of our study was to investigate the effect of ivabradine-induced reduction of afferent signalization from the heart on neuroendocrine stress response.

Methods: Male Sprague-Dawley rats (250 - 300 g) were injected with ivabradine (5 mg/kg body weight) or saline. Thirty minutes after ivabradine or saline administration animals were exposed to stressors (handling, restraint, or immobilization). Heart rate and blood pressure were recorded in rats by telemetry method. Moreover, blood samples were collected and plasma levels of catecholamines and corticosterone were determined.

Results: Administration of ivabradine attenuated stress-induced increase of heart rate and blood pressure in animals exposed to all three stressors. In rats exposed to the mild stressor, handling, ivabradine reduced secretion of epinephrine and norepinephrine compared to animals administered with saline. In contrast, in rats exposed to intense stressors (restraint or immobilization) ivabradine exaggerated epinephrine secretion, whereas plasma levels of norepinephrine were not significantly affected. Administration of ivabradine did not change plasma levels of corticosterone in animals exposed to handling, restraint or immobilization.

Conclusion: We have shown that ivabradine administration reduced the activity of the sympathetic nervous system during exposure to a mild stressor. In contrast, during exposure to intensive stressors, ivabradine increased the activity of adrenal medulla but without any effect on sympathetic nervous system activity. Hypothalamo-pituitary-adrenocortical axis activity remained unaffected after ivabradine treatment in animals exposed to stressors. Our findings indicate that selective reduction of heart rate during exposure to a mild psychosocial stressor might reduce sympathoadrenal stress response and therefore protect the organism from negative impact of stressors.

Keywords: afferent signalization; ivabradine; catecholamine; corticosterone; vagus nerve; heart rate; stress

Published: June 1, 2014  Show citation