Association between antiarrhythmic, electrophysiological and antioxidative effects of melatonin in ischemia/reperfusion

Melatonin is assumed to confer cardioprotective action via antioxidative properties. We evaluated the association between ventricular tachycardia and/or ventricular fibrillation (VT/VF) incidence, oxidative stress, and myocardial electrophysiological parameters in experimental ischemia/reperfusion under melatonin treatment. Melatonin was given to 28 rats (10 mg/kg/day, orally, for 7 days) and 13 animals received placebo. In the anesthetized animals, coronary occlusion was induced for 5 min followed by reperfusion with recording of unipolar electrograms from ventricular epicardium with a 64-lead array. Effects of melatonin on transmembrane potentials were studied in ventricular preparations of 7 rats in normal and ?ischemic? conditions. Melatonin treatment was associated with lower VT/VF incidence at reperfusion, shorter baseline activation times (ATs), and activation-repolarization intervals and more complete recovery of repolarization times (RTs) at reperfusion (less baseline-reperfusion difference, ΔRT) (p < 0.05). Superoxide dismutase (SOD) activity was higher in the treated animals and associated with ΔRT (p = 0.001), whereas VT/VF incidence was associated with baseline ATs (p = 0.020). In vitro, melatonin led to a more complete restoration of action potential durations and resting membrane potentials at reoxygenation (p < 0.05). Thus, the antioxidative properties of melatonin were associated with its influence on repolarization duration, whereas the melatonin-related antiarrhythmic effect was associated with its oxidative stress-independent action on ventricular activation.Fil: Sedova, Ksenia A.. Czech Technical University In Prague; República ChecaFil: Bernikova, Olesya G.. Ural Branch of Russian Academy of Sciences; RusiaFil: Cuprova, Julia I.. Czech Technical University In Prague; República ChecaFil: Ivanova, Alexandra D.. Lomonosov Moscow State University; RusiaFil: Kutaeva, Galina A.. Pitirim Sorokin Syktyvkar State University; RusiaFil: Pliss, Michael G.. Almazov National Medical Research Centre; RusiaFil: Lopatina, Ekaterina V.. University of Saint Petersburg; RusiaFil: Vaykshnorayte, Marina A.. Ural Branch Of Russian Academy Of Sciences; RusiaFil: Diez, Emiliano Raúl. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina. Universidad Nacional de Cuyo. Facultad de Ciencias Medicas. Instituto de Fisiologia; ArgentinaFil: Azarov, Jan E.. Ural Branch of Russian Academy of Sciences; Rusia. Pitirim Sorokin Syktyvkar State University; Rusi

Arterial baroreceptor reflex counteracts long-term blood pressure increase in the rat model of renovascular hypertension.

INTRODUCTION: The present study tested the hypothesis that long-term effects of baroreceptor activation might contribute to the prevention of persistent arterial blood pressure (BP) increase in the rat model of renovascular hypertension (HTN). METHODS: Repetitive arterial baroreflex (BR) testing was performed in normo- and hypertensive rats. The relationship between initial arterial BR sensitivity and severity of subsequently induced two-kidney one-clip (2K1C) renovascular HTN was studied in Wistar rats. Additionally, the time course of changes in systolic BP (SBP) and cardiac beat-to-beat (RR) interval was studied for 8 weeks after the induction of 2K1C renovascular HTN in the rats with and without sinoaortic denervation (SAD). In a separate experimental series, cervical sympathetic nerve activity (cSNA) was assessed in controls, 2K1C rats, WKY rats, and SHR. RESULTS: The inverse correlation between arterial BR sensitivity and BP was observed in the hypertensive rats during repetitive arterial BR testing. The animals with greater initial arterial BR sensitivity developed lower BP values after renal artery clipping than those with lower initial arterial BR sensitivity. BP elevation during the first 8 weeks of renal artery clipping in 2K1C rats was associated with decreased sensitivity of arterial BR. Although SAD itself resulted only in greater BP variability but not in persistent BP rise, the subsequent renal artery clipping invariably resulted in the development of sustained HTN. The time to onset of HTN was found to be shorter in the rats with SAD than in those with intact baroreceptors. cSNA was significantly greater in the 2K1C rats than in controls. CONCLUSIONS: Arterial BR appears to be an important mechanism of long-term regulation of BP, and is believed to be involved in the prevention of BP rise in the rat model of renovascular HTN

The relationship between baroreflex (BR) sensitivity and systolic blood pressure (SBP) in the pooled samples of Wistar rats with stable hypertension (n = 10) and without hypertension (n = 10) 8 weeks after induction of two-kidney one-clip renovascular hypertension.

<p>The inverse correlation between BR sensitivity and SBP is observed (r = 0.69, <i>p</i><0.01).</p

Experimental design.

<p>A: Series 1, evaluation of baroreflex function and time course of blood pressure changes after induction of two-kidney one-clip renovascular hypertension, as well as at investigation of the relationship between initial baroreflex sensitivity and severity of renovascular hypertension. B: Series 2, effect of sinoaortic denervation on the incidence and time to onset of two-kidney one-clip hypertension. C: Series 3, assessment of cervical sympathetic nerve activity in normo- and hypertensive animals. BP, blood pressure; BR, arterial baroreflex; cSNA, cervical sympathetic nerve activity; HTN, hypertension; 2K1C, two-kidney one-clip; MBP, mean blood pressure; RR, cardiac beat-to-beat interval; SAD, sinoaortic denervation; SBP, systolic blood pressure; SHR, spontaneously hypertensive rats; WKY, Wistar-Kyoto rats.</p

Cervical sympathetic nerve activity (left) and integrated electrical activity of cervical sympathetic nerve (right).

<p>A: Normotensive Wistar rats (n = 6). B: Wistar rats with two-kidney one-clip renovascular hypertension (n = 6). C: Wistar-Kyoto rats (n = 6). D: Spontaneously hypertensive rats (n = 7).</p

Systolic blood pressure and cardiac beat-to-beat interval over 8 weeks after left renal artery clipping in Wistar rats.

*<p><i>p</i><0.05 versus controls.</p

The relative contribution of low-, mid-, and high-amplitude integrated activity in the cervical sympathetic nerve (in percentage to total electrical activity) in the experimental groups.

<p>2K1C – Wistar rats with 2-kidney 1-clip renovascular hypertension; WKY – Wistar-Kyoto rats; SHR – spontaneously hypertensive rats.</p

Hemodynamic parameters in the animals with sinoaortic denervation.

<p>A: Systolic blood pressure (SBP) and B: Cardiac beat-to-beat (RR) interval before and after renal artery clipping in the rats with sinoaortic denervation. BV, baseline value; BP, blood pressure. *<i>p</i><0.05 versus baseline.</p