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beta(3)-adrenoceptor deficiency blocks nitric oxide-dependent inhibition of myocardial contractility.

Publication ,  Journal Article
Varghese, P; Harrison, RW; Lofthouse, RA; Georgakopoulos, D; Berkowitz, DE; Hare, JM
Published in: J Clin Invest
September 2000

The cardiac beta-adrenergic pathway potently stimulates myocardial performance, thereby providing a mechanism for myocardial contractile reserve. beta-Adrenergic activation also increases cardiac nitric oxide (NO) production, which attenuates positive inotropy, suggesting a possible negative feedback mechanism. Recently, in vitro studies suggest that stimulation of the beta(3)-adrenoceptor results in a negative inotropic effect through NO signaling. In this study, using mice with homozygous beta(3)-adrenoceptor deletion mutations, we tested the hypothesis that the beta(3)-adrenoceptor is responsible for beta-adrenergic activation of NO. Although resting indices of myocardial contraction were similar, beta-adrenergic-stimulated inotropy was increased in beta(3)(-/-) mice, and similar hyper-responsiveness was seen in mice lacking endothelial NO synthase (NOS3). NOS inhibition augmented isoproterenol-stimulated inotropy in wild-type (WT), but not in beta(3)(-/-) mice. Moreover, isoproterenol increased myocardial cGMP in WT, but not beta(3)(-/-), mice. NOS3 protein abundance was not changed in beta(3)(-/-) mice, and cardiac beta(3)-adrenoceptor mRNA was detected in both NOS3(-/-) and WT mice. These findings indicate that the beta(3)-adrenergic subtype participates in NO-mediated negative feedback over beta-adrenergic stimulation.

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Published In

J Clin Invest

DOI

ISSN

0021-9738

Publication Date

September 2000

Volume

106

Issue

5

Start / End Page

697 / 703

Location

United States

Related Subject Headings

  • Sympathetic Nervous System
  • Receptors, Adrenergic, beta-3
  • Receptors, Adrenergic, beta
  • Nitric Oxide Synthase Type III
  • Nitric Oxide Synthase Type II
  • Nitric Oxide Synthase
  • Nitric Oxide
  • Myocardial Contraction
  • Mice, Mutant Strains
  • Mice
 

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Varghese, P., Harrison, R. W., Lofthouse, R. A., Georgakopoulos, D., Berkowitz, D. E., & Hare, J. M. (2000). beta(3)-adrenoceptor deficiency blocks nitric oxide-dependent inhibition of myocardial contractility. J Clin Invest, 106(5), 697–703. https://doi.org/10.1172/JCI9323
Varghese, P., R. W. Harrison, R. A. Lofthouse, D. Georgakopoulos, D. E. Berkowitz, and J. M. Hare. “beta(3)-adrenoceptor deficiency blocks nitric oxide-dependent inhibition of myocardial contractility.J Clin Invest 106, no. 5 (September 2000): 697–703. https://doi.org/10.1172/JCI9323.
Varghese P, Harrison RW, Lofthouse RA, Georgakopoulos D, Berkowitz DE, Hare JM. beta(3)-adrenoceptor deficiency blocks nitric oxide-dependent inhibition of myocardial contractility. J Clin Invest. 2000 Sep;106(5):697–703.
Varghese, P., et al. “beta(3)-adrenoceptor deficiency blocks nitric oxide-dependent inhibition of myocardial contractility.J Clin Invest, vol. 106, no. 5, Sept. 2000, pp. 697–703. Pubmed, doi:10.1172/JCI9323.
Varghese P, Harrison RW, Lofthouse RA, Georgakopoulos D, Berkowitz DE, Hare JM. beta(3)-adrenoceptor deficiency blocks nitric oxide-dependent inhibition of myocardial contractility. J Clin Invest. 2000 Sep;106(5):697–703.

Published In

J Clin Invest

DOI

ISSN

0021-9738

Publication Date

September 2000

Volume

106

Issue

5

Start / End Page

697 / 703

Location

United States

Related Subject Headings

  • Sympathetic Nervous System
  • Receptors, Adrenergic, beta-3
  • Receptors, Adrenergic, beta
  • Nitric Oxide Synthase Type III
  • Nitric Oxide Synthase Type II
  • Nitric Oxide Synthase
  • Nitric Oxide
  • Myocardial Contraction
  • Mice, Mutant Strains
  • Mice