Effect of nitric oxide on cholinoreceptors of heart of animals at damage by adrenaline in terms of sex and activity of the gonads


  • Марія Романівна Хара Ternopil Volodymyr Hnatiuk National Pedagogical University 2 Maxyma Kryvonosa str., Ternopil, Ukraine, 46027, Ukraine
  • Олег Володимирович Кузів I.Ya. Horbachevsky Ternopil State Medical University 19A Glyboka str., Ternopil, Ukraine, 46000, Ukraine
  • Володимир Євгенович Пелих I.Ya. Horbachevsky Ternopil State Medical University 3 Chekhov str., Ternopil, Ukraine, 46000, Ukraine




acetylcholine, bradycardia duration, bradycardia intensity, regulation, gender, adrenaline myocardial damage, gonadectomy, substitutive hormonotherapy, nitric oxide


Methods. Experiments are conducted on 216 white mature rats of both sexes (180–240 g), which is modeled adrenaline myocardial damage (AMD) by intramuscular epinephrine administration (1 mg/kg). Activity of synthesis of nitric oxide is changed by administration of L-arginine donator (600 mg/kg) and non-selective inhibitor L-NAME (25 mg/kg) in the abdomen for 15 minutes to AMD reproduction [4]. Gonadectomy is performed surgically. Hormone replacement therapy after gonadectomy is conducted in females by administration of hexestrol (0.1 mg/kg) and progesterone (5 mg / rat), and in males – administration of testosterone (200 mg/100 g). [5, 6]. Research of heart sensitivity to exogenous acetylcholine animals is performed after administration of solution of acetylcholine chloride in the jugular vein. Chronotropic effect was assessed in intensity and duration of occurred bradycardia. Research of heart sensitivity to endogenous acetylcholine is performed by analyzing changes in heart rate at an electrical stimulation of the right vagus nerve [4]. The effect was evaluated by the intensity of bradycardia.

Results. Against the background of the administration of L-arginine, especially in the development of necrotic damage, deficiency of sex hormones increases the sensitivity of myocardial cholinergic receptors in males (IBah increased by 39% in the control, 5.7 and 3.2 times at 1 and 24 hours of experience) and a completely different reaction in females - a decline of 26.4% (in control) 2.1 times to 1 hour and increased 2.1 times in 24 hours. Using L-NAME, change the background of hormones does not affect the sensitivity of cholinergic receptors, while the intensity of the release of acetylcholine in the synaptic cleft (the electrical stimulation n.Vagus) in females in a much greater extent than in males increase at gonadectomy, including development of adrenaline myocardial damage.

Conclusions. Males and females respond differently to change the sensitivity of cholinergic receptors and the intensity of the release of the neurotransmitter acetylcholine in the presynaptic cleft when used donator blocker system and nitric oxide. Gonadectomy showed a direct relationship of influence of nitric oxide system on the heart condition of cholinergic regulation of sex hormones, which showed excellent dynamics change. Substitutive hormonotherapy most approximates the laws of choline reactivity of the heart, especially in the development of necrotic myocardium in the process to natural (under conditions of normal sex hormones)

Author Biographies

Марія Романівна Хара, Ternopil Volodymyr Hnatiuk National Pedagogical University 2 Maxyma Kryvonosa str., Ternopil, Ukraine, 46027

Doctor of medical science, professor

Department of health, physical rehabilitation and life 

Олег Володимирович Кузів, I.Ya. Horbachevsky Ternopil State Medical University 19A Glyboka str., Ternopil, Ukraine, 46000

Assistant professor

Department of general and minimally invasive surgery

Володимир Євгенович Пелих, I.Ya. Horbachevsky Ternopil State Medical University 3 Chekhov str., Ternopil, Ukraine, 46000

Candidate of Medical Sciences


Ondicova, K., Mravec, B. (2010). Multilevel interactions between the sympathetic and parasympathetic nervous systems: a minireview. Endo, 44 (2), 69–75. doi: 10.4149/endo_2010_02_69

Tracey, K. J. (2007). Physiology and immunology of the cholinergic antiinflammatory pathway. Journal of Clinical Investigation, 117 (2), 289–296. doi: 10.1172/jci30555

Xiong, J., Xue, F. S., Xu, Y. C., Yang, Q. Y., Liao, X., & Wang, W. L. (2009). Cholinergic agonists may produce preservation of myocardial ischaemia/reperfusion injury. Medical Hypotheses, 73 (3), 312–314. doi: 10.1016/j.mehy.2009.03.026

Bae, S. (2005). Gender Differences in Cardioprotection against Ischemia/Reperfusion Injury in Adult Rat Hearts: Focus on Akt and Protein Kinase C Signaling. Journal of Pharmacology and Experimental Therapeutics, 315 (3), 1125–1135. doi: 10.1124/jpet.105.090803

Perusquia, M. (2005). Androgens Induce Relaxation of Contractile Activity in Pregnant Human Myometrium at Term: A Nongenomic Action on L-Type Calcium Channels. Biology of Reproduction, 73 (2), 214–221. doi: 10.1095/biolreprod.104.036954

Yaron, M., Greenman, Y., Rosenfeld, J. B., Izkhakov, E., Limor, R., Osher, E. et. al. (2009). Effect of testosterone replacement therapy on arterial stiffness in older hypogonadal men. European Journal of Endocrinology, 160 (5), 839–846. doi: 10.1530/eje-09-0052

Laughlin, G. A., Barrett-Connor, E., Bergstrom, J. (2008). Low Serum Testosterone and Mortality in Older Men. The Journal of Clinical Endocrinology & Metabolism, 93 (1), 68–75. doi: 10.1210/jc.2007-1792

Smetnik, V. P., Ilina, L. M. (2007). Hypertension in women in perimenopausal and postmenopausal women (Part I) (Sexual features and the role of estrogen deficiency). Menopause, 1, 5–9.

Tikhomirov, A. L. (2007). Hormone replacement therapy in postmenopausal women physiological and surgical. Farmateka, 10, 37–41.

Bolego, C., Vegeto, E., Pinna, C., Maggi, A. (2006). Selective agonists of estrogen reseptor isoforms. Arteriosclerosis, Thrombosis, and Vascular Biolog, 26, 2192–2199.

Fellet, A. L. (2006). Autonomic regulation of pacemaker activity: role of heart nitric oxide synthases. AJP: Heart and Circulatory Physiology, 291 (3), 1246–1254. doi: 10.1152/ajpheart.00711.2005

Moncada, S., Higgs, E. A. (2006). The discovery of nitric oxide and its role in vascular biology. British Journal of Pharmacology, 147 (1), 193–201. doi: 10.1038/sj.bjp.0706458

Moibenko, A. A., Sagach, V. F., Tkachenko, M. N. et al. (2004). The fundamental mechanisms of action of nitric oxide on the cardiovascular system as the basis of pathogenetic treatment of diseases. Physiol. Zh., 50 (1), 11–30.

Loyer, X., Damy, T., Chvojkova, Z., Robidel, E., Marotte, F., Oliviero, P. et. al. (2007). 17β-Estradiol Regulates Constitutive Nitric Oxide Synthase Expression Differentially in the Myocardium in Response to Pressure Overload. Endocrinology, 148 (10), 4579–4584. doi: 10.1210/en.2007-0228

Khara, M. R., Pelyh, V. E. (2009). Influence of castration and Hormonal replacement therapy on the performance of mathematical analysis of heart rhythm damaged adrenaline female rats. Bulletin of scientific research, 3, 74–76.

Khara, M. R., Dorohina, A. M. (2010). Nitric oxide and cardiovascular system (literature review). Achievements clinical and expert. med., 12 (1), 14–19.

Khara, M. R. (2004). Influence of castration on heart cholinergic response of rats of different sex in the development of adrenal myocardiodystrophy. Journal of scientific researches, 1, 91–93.