+ Site Statistics
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

Selective beta 1-adrenoceptor blockade enhances positive inotropic responses to endogenous catecholamines mediated through beta 2-adrenoceptors in human atrial myocardium



Selective beta 1-adrenoceptor blockade enhances positive inotropic responses to endogenous catecholamines mediated through beta 2-adrenoceptors in human atrial myocardium



Circulation Research 66(6): 1610-1623



We determined the relative contribution of beta 1- and beta 2-adrenoceptor stimulation to the positive inotropic responses of human atrial myocardium to catecholamines. (-)Norepinephrine produced stimulation predominantly through beta 1-receptors and (-)epinephrine through both beta 1- and beta 2-receptors. However, there were marked differences in the responses of tissues from patients treated with the beta 1-selective antagonist atenolol compared with non-beta-blocker-treated patients; surprisingly, beta 2-mediated responses were enhanced, and beta 1-mediated responses were unaltered. There was an enhanced responsiveness to (-)epinephrine (atenolol treated: -log M EC50, 7.57 +/- 0.07; non-beta-blocker treated: -log M EC50, 6.77 +/- 0.17; p less than 0.001), and the relative importance of beta 2-adrenoceptor stimulation was increased for both (-)norepinephrine and (-)epinephrine. In tissues from atenolol-treated patients, salbutamol, a beta 2-selective partial agonist, had an enhanced potency and a greater intrinsic activity (atenolol treated: -log M EC50, 7.13 +/- 0.09; intrinsic activity, 0.86 +/- 0.04; non-beta-blocker treated: -log M EC50, 5.76 +/- 0.44; intrinsic activity, 0.39 +/- 0.13). We investigated possible mechanisms underlying the enhanced responsiveness to beta 2 stimulation. Determination of beta 2-adrenoceptor affinity for salbutamol showed no change of affinity in atenolol-treated patients. Responses of the tissues to the cyclic AMP analogue dibutyryl cyclic AMP were not different between atenolol-treated and non-beta-blocker-treated patients. The results suggest that chronic blockade of beta 1-adrenoceptors causes enhanced coupling of beta 2-adrenoceptors to adenylate cyclase or to other mechanisms leading to increased contractile force.

Please choose payment method:






(PDF emailed within 1 workday: $29.90)

Accession: 041322128

Download citation: RISBibTeXText

PMID: 1971535


Related references

Selective beta 1-adrenoceptor blockade enhances positive inotropic responses to endogenous catecholamines mediated through beta 2- adrenoceptors in human atrial myocardium. Circulation Research 66(6): 1610-1623, 1990

Inhibition by 5-hydroxytryptamine of the beta adrenoceptor-mediated positive inotropic responses to catecholamines in rabbit papillary muscles: direct interaction with beta adrenoceptors. Journal of Pharmacology and Experimental Therapeutics 261(3): 1160-1166, 1992

Enoximone potentiates the positive inotropic effects of beta 1 adrenoceptor and beta 2 adrenoceptor stimulation in human atrial myocardium. Cardiology 77(Suppl. 3): 14-20, 1990

Xamoterol activates beta 1 but not beta 2 adrenoceptors in mammalian myocardium comparison of its affinity for beta 1 and beta 2 adrenoceptors coupled to the adenylate cyclase in feline and human ventricle with positive inotropic effects. Journal of Cardiovascular Pharmacology 13(1): 105-117, 1989

Cilostamide potentiates more the positive inotropic effects of (-)-adrenaline through beta(2)-adrenoceptors than the effects of (-)-noradrenaline through beta (1)-adrenoceptors in human atrial myocardium. Naunyn-Schmiedeberg's Archives of Pharmacology 374(3): 249-253, 2006

Enoximone potentiates the positive inotropic effects of beta-1- and beta-2-adrenoceptor stimulation in human atrial myocardium. Cardiology 77(Suppl. 3): 14-20; Discussion 27-33, 1990

Enoximone Potentiates the Positive Inotropic Effects of Beta-1- and Beta-2-Adrenoceptor Stimulation in Human Atrial Myocardium. Cardiology 77(3): 14-20, 1990

Regional differences of beta 1 adrenoceptor mediated and beta 2 adrenoceptor mediated functions in feline heart a beta 2 adrenoceptor mediated positive inotropic effect possibly unrelated to cyclic amp. Naunyn-Schmiedeberg's Archives of Pharmacology 344(1): 56-69, 1991

Spare receptors for beta-adrenoceptor-mediated positive inotropic effects of catecholamines in the human heart. Journal of Cardiovascular Pharmacology 19(2): 222-232, 1992

Ibopamine mediates positive inotropic effects via beta 1 and beta 2 adrenoceptors in the human myocardium. Naunyn-Schmiedeberg's Archives of Pharmacology 345(Suppl. 1): R72, 1992

-Adrenoceptors and -Adrenoceptor-Mediated Positive Inotropic Effects in Failing Human Myocardium. Journal of Cardiovascular Pharmacology 12(3): 357-364, 1988

Chronic beta 1 adrenoceptor blockage enhances positive inotropic responses to 5 hydroxytryptamine in human atrium. Journal of Molecular & Cellular Cardiology 22(Suppl. 3): S2, 1990

Differential effects of cocaine on the positive inotropic effect of noradrenaline mediated by alpha1- and beta-adrenoceptors in failing human myocardium. European Journal of Pharmacology 419(2-3): 223-230, 2001

Differential recruitment of alpha 1- and beta-adrenoceptors in inotropic control of atrial child myocardium by endogenous noradrenaline. Acta Physiologica Scandinavica 170(1): 21-31, 2000

Potentiation by enoximone of selective beta 1 adrenoceptor and beta 2 adrenoceptor stimulation in human atrial myocardium. British Journal of Pharmacology 9(Suppl.): 202P, 1989