Involvement of alpha-adrenergic receptors in the regulation of inotropy in the isolated rat heart

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Abstract

Background. Although activation of α1-adrenergic receptors is not required for myocardial contractility, α1-adrenergic receptors can provide significant support for myocardial inotropy in various heart diseases.

Aim. To study the participation of α1A- and α1B-adrenergic receptors in the force contraction regulation of the left ventricle of an isolated rat heart.

Material and methods. Isolated hearts of 20-week-old rats were perfused with Krebs–Henseleit solution according to the Langendorff method. The most important indicator of the inotropic function of the heart, the pressure developed by the left ventricle, was recorded using a latex balloon placed in the cavity of the left ventricle. At the 1st stage of the work, the effects of blockers of α1-adrenergic receptor subtypes on the force of contractions of an isolated heart were evaluated. At the 2nd stage, the effect of non-selective stimulation of α1-adrenergic receptors by methoxamine was studied. At the 3rd stage, the effect of methoxamine was evaluated against the background of selective blockade of α1A- or α1B-adrenergic receptors. Statistical analysis of data was performed using Statistica 6.0 software. The significance of changes between dependent data was assessed using the Wilcoxon test. To assess the differences between two sets of independent data, the Mann–Whitney U-test was used. Changes were considered statistically significant at p <0.05.

Results. Infusion of the α1A-adrenergic blocker WB4101 at a concentration of 10–6 mol/l led to an increase in the force of contraction of the isolated heart by 5.6% (p=0.048). Blocker of α1B-adrenergic receptors chloroethylclonidine dihydrochloride at a concentration of 10–8 mol/l caused a decrease in the force of contraction of the heart by 15% (p=0.046). Stimulation of α1A-adrenergic receptors with methoxamine (10–8 mol/l) led to a decrease in pressure developed by the left ventricle of an isolated heart by 47% (p=0.002). Preliminary blockade of α1A-adrenergic receptors significantly reduced the severity of the negative inotropic effect of methoxamine on the left ventricular myocardium. Preliminary blockade of α1B-adrenergic receptors changed the direction of the inotropic effect of methoxamine on the myocardium of the left ventricle of an isolated heart.

Conclusion. Non-selective stimulation of α1-adrenergic receptors by methoxamine leads to a significant decrease in cardiac inotropy, while preliminary blockade of α1A- or α1B-adrenergic receptors reduces the severity of this effect.

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About the authors

Insaf I. Khabibrakhmanov

Kazan (Volga Region) Federal University

Author for correspondence.
Email: insaf1201@mail.ru
ORCID iD: 0000-0001-5494-6553

Сand. Sci. (Biol.), Assoc. Prof., Depart. of Human Health Protection, Institute of Fundamental Medicine and Biology

Russian Federation, Kazan, Russia

Andrey L. Zefirov

Kazan State Medical University

Email: zefirovtl@mail.ru
ORCID iD: 0000-0001-7436-7815

M.D., D. Sci. (Med.), Academician of Russian Academy of Sciences, Prof., Depart. of Physiology

Russian Federation, Kazan, Russia

Nafisa I. Ziyatdinova

Kazan (Volga Region) Federal University

Email: NIZiyatdinova@kpfu.ru
ORCID iD: 0000-0002-4503-7451

Doct. Sci. (Biol.), Prof., Depart. of Human Health Protection, Institute of Fundamental Medicine and Biology

Russian Federation, Kazan, Russia

Marat A. Mukhamedyarov

Kazan State Medical University

Email: marat.muhamedyarov@kazangmu.ru
ORCID iD: 0000-0002-0397-9002

M.D., D. Sci. (Med.), Assoc. Prof., Head of Depart., Depart. of Physiology

Russian Federation, Kazan, Russia

Timur L. Zefirov

Kazan (Volga Region) Federal University

Email: Timur.Zefirov@kpfu.ru
ORCID iD: 0000-0001-9557-1639

M.D., D. Sci. (Med.), Prof., Head of Depart., Depart. of Human Health Protection, Institute of Fundamental Medicine and Biology

Russian Federation, Kazan, Russia

References

  1. Akinaga J, García-Sáinz A, Pupo AS. Updates in the function and regulation of α1-adrenoceptors. Br J Pharmacol. 2019;176(14):2343–2357. doi: 10.1111/bph.14617.
  2. Myagmar BE, Flynn JM, Cowley PM, Swigart PM, Montgomery MD, Thai K, Nair D, Gupta R, Deng DX, Hosoda C, Melov S, Baker AJ, Simpson PC. Adrenergic receptors in individual ventricular myocytes: The beta-1 and alpha-1B are in all cells, the alpha-1A Is in a subpopulation, and the beta-2 and beta-3 are mostly absent. Circ Res. 2017;120(7):1103–1115. doi: 10.1161/CIRCRESAHA.117.310520.
  3. Luther H, Podlowski S, Schulze W, Morwinski R, Buchwalow I, Baumann G, Wallukat G. Expression of alpha1-adrenergic receptor subtypes in heart cell culture. Mol Cell Biochem. 2001;224(1–2):69–79. doi: 10.1023/A:1011991117624.
  4. Thomas RC, Cowley PM, Singh A, Myagmar BE, Swigart PM, Baker AJ, Simpson PC. The alpha-1A adrenergic receptor in the rabbit heart. PLoS ONE. 2016;11(6):e0155238. doi: 10.1371/journal.pone.0155238.
  5. Filippi S, Parenti A, Donnini S, Granger HJ, Fazzini A, Ledda F. Alpha(1D)-adrenoceptors cause endothelium-dependent vasodilatation in the rat mesenteric vascular bed. J Pharmacol Exp Ther. 2001;296:869–875. PMID: 11181918.
  6. Chinkin AS. The adrenaline/noradrenaline and alpha/beta-adrenoreceptor ratios in the myocardium, and the adrenergic chrono- and inotropic reactions in extreme states and adaptation. Science and sport: current trends. 2014;4(3):10–18. (In Russ.)
  7. Phan D, Stratton MS, Huynh QK, McKinsey TA. A novel protein kinase C target site in protein kinase D is phosphorylated in response to signals for cardiac hypertrophy. Biochem Biophys Res Commun. 2011;411(2):335–341. doi: 10.1016/j.bbrc.2011.06.143.
  8. Janssen PML, Canan BD, Kilic A, Whitson BA, Baker AJ. Human myocardium has a robust α1A-subtype adrenergic receptor inotropic response. J Cardiovasc Pharmacol. 2018;72(3):136–142. doi: 10.1097/FJC.0000000000000604.
  9. Nozdrachyov AD, Tsirkin VI, Korotaeva YV. The role of alpha1-adrenoreceptors for activity of the heart in humans and animals. Part 1 (Review). Russian journal of physiology. 2016;102(2):130–145. (In Russ.)
  10. Khabibrakhmanov II, Ziyatdinova NI, Khisamieva LI, Krulova AV, Zefirov TL. Age-related features influence of alpha(1)-adrenoreceptor stimulation on isolated rat heart. Biosc Biotech Res Comm. 2019;12(5):351–354.
  11. Khabibrakhmanov II, Ziyatdinova NI, Khisamieva LI, Biktemirova RG, Zefirov TL. Alpha(1А)-adrenoreceptor participation in myocardial contractility regulation among newborn rats. Plant Archives. 2019;19(2):2188–2192.
  12. Zhang S, Takahashi R, Yamashita N, Teraoka H, Kitazawa T. Αlpha1B-adrenoceptor-mediated positive inotropic and positive chronotropic actions in the mouse atrium. Eur J Pharmacol. 2018;839:82–88. doi: 10.1016/j.ejphar.2018.08.038.
  13. Zefirov TL, Khabibrakhmanov II, Galieva AM, Sungatullina MI, Ziyatdinova NI. The influence of alpha 1A-ARs inhibition on the isolated heart chronotropy and coronary flow. European Journal of Clinical Investigation. 2019;49:144–145.
  14. O’Connell TD, Jensen BC, Baker AJ, Simpson PC. Cardiac alpha1-adrenergic receptors: Novel aspects of expression, signaling mechanisms, physiologic function, and clinical importance. Pharmacol Rev. 2014;66(1):308–333. doi: 10.1124/pr.112.007203.
  15. Chu C, Thai K, Park KW, Wang P, Makwana O, Lovett DH, Simpson PC, Baker AJ. Intraventricular and interventricular cellular heterogeneity of inotropic responses to α1-adrenergic stimulation. Am J Physiol Heart Circ Physiol. 2013;304(7):946–953. doi: 10.1152/ajpheart.00822.2012.

Supplementary files

Supplementary Files
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1. JATS XML
2. Fig. 1. Dynamics of the left ventricular developed pressure (LVDP) in the isolated rat heart during perfusion with WB4101 and chloroethylclonidine (CEC) dihydrochloride. *Significance of changes compared with baseline.

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3. Fig. 2. Dynamics of the left ventricular developed pressure (LVDP) of the isolated rat heart during sequential perfusion with methoxamine after the administration of WB4101 and chloroethylclonidine (CEC) dihydrochloride. *Significance of changes compared with baseline. #Significance of changes compared with the control group (methoxamine).

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