Stimulation of α1-adrenoreceptors inhibits myocardial contractility in rats

T.L. Zefirov a, I.I. Khabibrakhmanov a, J.V. Valeeva a, J.T. Zefirova b,c, N.I. Ziyatdinova a

a Kazan Federal University, Kazan, 420008 Russia

b Saint Mary's Hospital, Trinity Health of New England, Hartford, CT, 06105 USA

с Yale School of Medicine, New Haven, CT, 06510 USA

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Abstract

The exact role of ?Б1-adrenoreceptors (?Б1-AR) as myocardial contractility modulators is still not clear. We studied the effects of ?Б1-AR stimulation with methoxamine hydrochloride (Sigma) on the myocardial contractility ex vivo and in vitro: on the isolated heart (Langendorff's model) and on the atrium and ventricular myocardium strips in rats, respectively. The experiments were performed on random-bred albino 20-week-old rats (n = 28) with the average weight of 200–250 g. The contractility force (F) of myocardium strips was measured in grams (g). The contractility of isolated heart was measured as pressure in the left ventricle (mm Hg). All the studied concentrations of methoxamine (10–9–10–6 §?) inhibited the contractility of the myocardium strips of rats' atria and ventricles. The stimulation of ?Б1-AR with methoxamine (10–9 and 10–8 §?) led to a decrease in the left ventricular pressure of the isolated heart in rats. The intensity of the negative inotropic effects was proportionate to the agonist concentration.

Keywords: ?Б1-adrenoreceptors, heart, myocardial contractility, rats

Acknowledgments. The work is performed according to the Russian Government Program of Competitive Growth of Kazan Federal University and supported by the Russian Foundation for Basic Research and the Government of the Republic of Tatarstan (project no. 18-44-160022).

References

  1. Brodde O.E., Bruck H., Leineweber K. Cardiac adrenoceptors: Physiological and pathophysiological relevance. J. Pharmacol. Sci., 2006, vol. 100, no. 5, pp. 323–337. doi: 10.1254/jphs.CRJ06001X.
  2. Metz L.D., Seidler F.J., McCook E.C., Slotkin T.A. Cardiac alpha-adrenergic receptor expression is regulated by thyroid hormone during a critical developmental period. J. Mol. Cell. Cardiol., 1996, vol. 28, no. 5, pp. 1033–1044. doi: 10.1006/jmcc.1996.0096.
  3. Jensen B.C., O'Connell T.D., Simpson P.C. Alpha-1-adrenergic receptors: Targets for agonist drugs to treat heart failure. J. Mol. Cell. Cardiol., 2011, vol. 51, no. 4, pp. 518–528. doi: 10.1016/j.yjmcc.2010.11.014.
  4. Simpson P. Lessons from knockouts: The alpha1-ARs. In: Perez D.M. (Ed.) The Adrenergic Receptors in the 21st Century. Totowa, N. J., Hum, Press. 2006, pp. 207–240.
  5. Tanoue A., Nasa Y., Koshimizu T., Shinoura H., Oshikawa S., Kawai T., Sunada S., Takeo S., Tsujimoto G. The ?Б1D-adrenergic receptor directly regulates arterial blood pressure via vasoconstriction. J. Clin. Invest., 2002, vol. 109, no. 6, pp. 765–775. doi: 10.1172/JCI14001.
  6. Hirano S., Kusakari Y., O-Uchi J., Morimoto S., Kawai M., Hongo K., Kurihara S. Intracellular mechanism of the negative inotropic effect induced by alpha1-adrenoceptor stimulation in mouse myocardium. J. Physiol. Sci., 2006, vol. 56, no. 4, pp. 297−304. doi: 10.2170/physiolsci.RP007306.
  7. Tsirkin V.I., Korotaeva Yu.V. The role of protein kinase A, B, C and D in the regulation of cardiomyocyte contractility (Review). Report I. Vestn. Sev. (Arkt.) Fed Univ. Ser. Med.-Biol. Nauki, 2015, no. 2, pp. 53˗61. doi: 10.1042 / BJ20021626.
  8. Fu Y., Rubin C.S. Protein kinase D: Coupling extracellular stimuli to the regulation of cell physiology. EMBO Rep., 2011, vol. 12, no. 8, pp. 785−796. doi: 10.1038/embor.2011.139.
  9. Haworth R.S., Cuello F., Avkiran M. Regulation by phosphodiesterase isoforms of protein kinase A-mediated attenuation of myocardial protein kinase D activation. Basic Res. Cardiol., 2011, vol. 106, no. 1, pp. 51−63. doi: 10.1007/s00395-010-0116-1.
  10. Stathopoulou K., Cuello F., Candasamy A.J., Kemp E.M., Ehler E., Haworth R.S., Avkiran M. Four-and-a-half LIM domains proteins are novel regulators of the protein kinase D pathway in cardiac myocytes. Biochem. J., 2014, vol. 457, no. 3, pp. 451−461. doi: 10.1042/BJ20131026.
  11. Bardswell S.C., Cuello F., Rowland A.J., Sadayappan S., Robbins J., Gautel M., Walker J.W., Kentish J.C., Avkiran M. Distinct sarcomeric substrates are responsible for protein kinase D-mediated regulation of cardiac myofilament Ca2+ sensitivity and cross-bridge cycling. J. Biol. Chem., 2010, vol. 285, no. 8, pp. 5674−5682. doi: 10.1074/jbc.M109.066456.
  12. Kamp T.J., Hell J.W. Regulation of cardiac L-type calcium channels by protein kinase A and protein kinase C. Circ. Res., 2000, vol. 87, no. 12, pp. 1095−1102. doi: 10.1161/01.RES.87.12.1095.
  13. Nishimaru K., Tanaka Y., Tanaka H., Shigenobu K. Pharmacological evidence for involvement of phospholipase D, protein kinase C, and sodium-calcium exchanger in alpha-adrenoceptor-mediated negative inotropy in adult mouse ventricle. J. Pharmacol. Sci., 2003, vol. 92, no. 3, pp. 196–202. doi: 10.1254/jphs.92.196.
  14. Rang H. Pharmacology. Edinburgh, Churchill Livingstone, 2003. xii, 796 §в.
  15. Zefirov T.L., Khabibrakhmanov I.I., Ziyatdinova N.I., Zefirov A.L. Peculiar aspects in influence of ?Б1-adrenoceptor stimulation on isolated rat heart. Bull. Exp. Biol. Med., 2016, vol. 162, no. 1, pp. 4–6. doi: 10.1007/s10517-016-3530-z.
  16. Ziatdinova N.I., Zefirov A.L., Zefirov T.L. Opposite changes in cardiac chronotropy induced by selective blockade of ?Б1A-adrenoceptors in rats of different age. Bull. Exp. Biol. Med., 2011, vol. 152, no. 1, pp. 19˗21. doi: 10.1007/s10517-011-1442-5.
  17. Myslivecek J, NovЁўkovЁў M, Klein M. Receptor subtype abundance as a tool for effective intracellular signaling. Cardiovasc. Hematol. Disord.: Drug Targets, 2008, vol. 8, no. 1, pp. 66–79. doi: 10.2174/187152908783884939.

Received

June 25, 2018

 

Zefirov Timur L'vovich, Doctor of Medical Sciences, Professor, Department of Human Health Protection

Kazan Federal University

ul. Kremlevskaya, 18, Kazan, 420008 Russia

E-mail: zefirovtl@mail.ru

Khabibrakhmanov Insaf Ilkhamovich, Candidate of Biological Sciences, Senior Lecturer, Department of Human Health Protection

Kazan Federal University

ul. Kremlevskaya, 18, Kazan, 420008 Russia

E-mail: insaf1201@mail.ru

Valeeva Julia Vladimirovna, Candidate of Medical Sciences, Associate Professor, Department of Emergency Aid and Simulation Medicine

Kazan Federal University

ul. Kremlevskaya, 18, Kazan, 420008 Russia

E-mail: JVValeeva@kpfu.ru

Zefirova Julia Timurovna, Candidate of Medical Sciences

Saint Mary's Hospital; Trinity Health of New England

Hartford, CT, 061505 USA

Yale School of Medicine

New Haven, CT, 06510 USA

Ziyatdinova Nafisa Il'gizovna, Doctor of Biological Sciences, Professor, Department of Human Health Protection

Kazan Federal University

ul. Kremlevskaya, 18, Kazan, 420008 Russia

E-mail: nafisaz@mail.ru

 

For citation: Zefirov T.L., Khabibrakhmanov I.I., Valeeva J.V., Zefirova J.T., Ziyatdinova N.I. Stimulation of ?Б1-adrenoreceptors inhibits myocardial contractility in rats. Uchenye Zapiski Kazanskogo Universiteta. Seriya Estestvennye Nauki, 2018, vol. 160, no. 4, pp. 613–620.

Для цитирования: Zefirov T.L., Khabibrakhmanov I.I., Valeeva J.V., Zefirova J.T., Ziyatdinova N.I. Stimulation of α1-adrenoreceptors inhibits myocardial contractility in rats |/ Учен. зап. Казан. ун-та. Сер. Естеств. науки. – 2018. – Т. 160, кн. 4. – С. 613–620.

 

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