Skip to main content
Log in

Regional distribution of β1- and β2-adrenoceptors in the failing and nonfailing human heart

  • Originals
  • Published:
European Journal of Clinical Pharmacology Aims and scope Submit manuscript

Summary

Total β-adrenoceptor density and β1- and β2-subtype distribution in right and left atria and in different ventricular regions from 14 failing and seven nonfailing human hearts have been compared. End-stage heart failure was due to idiopathic dilated cardiomyopathy (n=8) or ischaemic cardiomyopathy (n=6).

In nonfailing hearts the total β-adrenoceptor density was similar in the right and left atria and in all the ventricular regions studied (about 70 to 80 fmol/mg protein). The β12-adrenoceptor ratio in both nonfailing atria was similar (about 70:30%) and was significantly smaller than in the different regions of both ventricles (about 80:20%). The β1-subtype density was similar in nonfailing atria and ventricles (about 55 fmol/mg protein). The β2-subtype density was significantly higher in the right and left atrium (about 25 fmol/mg protein) than in both ventricles (about 15 fmol/mg protein).

In patients with end-stage heart failure due to idiopathic dilated cardiomyopathy or ischaemic cardiomyopathy the total β-adrenoceptor density was reduced by 50–60% in all regions. On the other hand, the β1- and β2-subtype distribution differed with the cause of heart failure. In patients with idiopathic dilated cardiomyopathy, the β1-adrenoceptor density was lower in all regions, but the β2-adrenoceptor density was not significantly reduced. In patients with ischaemic cardiomyopathy both β1- and β2-adrenoceptors were reduced in all regions.

It is concluded that downregulation of β-adrenoceptors in patients with end-stage idiopathic dilated cardiomyopathy or ischaemic cardiomyopathy occurs uniformly throughout the heart. The results support the hypothesis that changes in β-adrenoceptor subtypes may be related to the cause of heart failure.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Böhm M, Prieske B, Schnabel P, Schwinger R, Kemkes B, Klövekorn WP, Erdmann E (1989) Reduced effects of dopexamine on force of contraction in the failing human heart despite preserved β2-adrenoceptor subpopulation. J Cardiovasc Pharmacol 14: 549–559

    Google Scholar 

  • Böhm M, Larisch A, Erdmann E (1991) Quantification of G by a novel radioimmunoassay in cardiomyopathic human heart. Arch Pharmacol 343 [Suppl]: R 54

  • Bradford MM (1976) A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 72: 248–254

    Google Scholar 

  • Bristow MR, Ginsburg R, Minobe W, Cubicciotti RS, Sageman W, Lurie K, Billingham ME, Harrison DC, Stinson EB (1982) Decreased catecholamine sensitivity and β-adrenergic-receptor density in failing human hearts. N Engl J Med 307: 205–211

    Google Scholar 

  • Bristow MR, Ginsburg R, Umans V, Fowler M, Monobe W, Rasmussen R, Zera P, Menlove R, Shah P, Jamieson S, Stinson EB (1986) β1- and β2-adrenergic-receptor subpopulations in nonfailing and failing human myocardium: coupling of both receptor subtypes to muscle contraction and selective β1-receptor down-regulation in heart failure. Circ Res 59: 297–309

    Google Scholar 

  • Bristow MR, Hershberger RE, Port JD, Gilbert EM, Sandoval A, Rasmussen R, Cates AE, Feldman AM (1990) β-adrenergic pathways in nonfailing and failing human ventricular myocardium. Circulation 82 [Suppl I]: I-12-I-25

    Google Scholar 

  • Bristow MR, Anderson FL, Port JD, Skerl L, Hershberger RE, Larrabee P, O'Connell JB, Renlund DG, Volkman K, Murray J, Feldman (1992) Uncoupling of β1-adrenergic receptors in ischemic dilated cardiomyopathy. Circulation (in press)

  • Brodde OE, O'Hara N, Zerkowski HR, Rohm N (1984) Human cardiac β-adrenoceptors: both β1- and β2-adrenoceptors are functionally coupled to the adenylate cyclase in right atrium. J Cardiovasc Pharmacol 6: 1184–1191

    Google Scholar 

  • Brodde OE, Schüler S, Kretsch R, Brinkmann M, Borst HG, Hetzer R, Reidemeister JC, Warnecke H, Zerkowski HR (1986) Regional distribution of β-adrenoceptors in the human heart: Coexistence of functional β1- and β2-adrenoceptors in both atria and ventricles in severe congestive cardiomyopathy. J Cardiovasc Pharmacol 8: 1235–1242

    Google Scholar 

  • Brodde OE (1987) Cardiac beta-adrenergic receptors. ISI Atlas Sci Pharmacol 1: 107–112

    Google Scholar 

  • Brodde OE, Zerkowski HR, Borst HG, Maier W, Michel MC (1989a) Drug- and disease-induced changes of human cardiac β1- and β2-adrenoceptors. Eur Heart J 10 [Suppl B]: 38–44

    Google Scholar 

  • Brodde OE, Zerkowski HR, Doetsch N, Motomura S, Khamssi M, Michel MC (1989b) Myocardial beta-adrenoceptor changes in heart failure: concomitant reduction in beta1- and beta2-adrenoceptor function related to the degree of heart failure in patients with mitral valve disease. J Am Coll Cardiol 14: 323–331

    Google Scholar 

  • Dickinson KEJ, Nahorski SR (1981) Identification of solubilised beta1 and beta2 adrenoceptors in mammalian lung. Life Sci 29: 2527–2533

    Google Scholar 

  • Dooley DJ, Bittiger H, Reymann NC (1986) CGP 2072A: a useful tool for quantitating β1- and β2-adrenoceptors. Eur J Pharmacol 130: 137–139

    Google Scholar 

  • Heitz A, Schwartz J, Velly J (1983) β-adrenoceptors of the human myocardium: determination of β1- and β2-subtypes by radioligand binding. Br J Pharmacol 80: 711–717

    Google Scholar 

  • Kaumann AJ, Lemoine H, Schwederski-Menke U, Ehle B (1989) Relations between β-adrenoceptor occupancy and increases of contractile force and adenylate cyclase activity induced by catecholamines in human ventricular myocardium. Arch Pharmacol 339: 99–112

    Google Scholar 

  • Lemoine H, Schönell H, Kaumann AJ (1988) Contribution of β1- and β2-adrenoceptors of human atrium and ventricle to the effects of noradrenaline and adrenaline as assessed with (-)-atenolol. Br J Pharmacol 95: 55–66

    Google Scholar 

  • McDevitt DG (1989) In vivo studies on the function of cardiac β-adrenoceptors in man. Eur Heart J 10 [Suppl B]: 22–28

    Google Scholar 

  • Michel MC, Pingsmann A, Beckeringh JJ, Zerkowski HR, Doetsch N, Brodde OE (1988) Selective regulation of β1- and β2-adrenoceptors in the human heart by chronic β-adrenoceptor antagonist treatment. Br J Pharmacol 94: 685–692

    Google Scholar 

  • Motomura S, Deighten NM, Zerkowski HR, Doetsch N, Michel MC, Brodde OE (1990) Chronic β1-adrenoceptor antagonist treatment sensitizes β2-adrenoceptors, but desensitizes M2-muscarinic receptors in the human right atrium. Br J Pharmacol 101: 363–369

    Google Scholar 

  • Scatchard G (1949) The attraction of proteins for small molecules and ions. Ann NY Acad Sci 51: 660–672

    Google Scholar 

  • Steinfath M, Geertz B, Schmitz W, Scholz H, Haverich A, Breil I, Hanrath P, Reupcke C, Sigmund M, Lo HB (1991) Distinct down-regulation of cardiac β1- and β2-adrenoceptors in different human heart diseases. Arch Pharmacol 343: 217–220

    Google Scholar 

  • Stiles GL, Taylor S, Lefkowitz RJ (1983) Human cardiac beta-adrenergic receptors: subtype heterogeneity delineated by direct radioligand binding. Life Sci 33: 467–473

    Google Scholar 

  • Summers RJ, Molenaar P, Russell F, Elnatan J, Jones CR, Buxton BF, Chang V, Hambley J (1989) Coexistence and localisation of β1- and β2-adrenoceptors in the human heart. Eur Heart J 10 [Suppl B]: 11–21

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Steinfath, M., Lavicky, J., Schmitz, W. et al. Regional distribution of β1- and β2-adrenoceptors in the failing and nonfailing human heart. Eur J Clin Pharmacol 42, 607–611 (1992). https://doi.org/10.1007/BF00265923

Download citation

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00265923

Key words

Navigation