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Related Experiment Video

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Location, Dissection, and Analysis of the Murine Stellate Ganglion
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beta2-Adrenoceptor gene variation and systemic vasodilatation during ganglionic blockade.

Christiane Hesse1, Darrell R Schroeder, Wayne T Nicholson

  • 1Department of Anaesthesiology, Internal Medicine, Mayo Clinic, Rochester, MN 55905, USA.

The Journal of Physiology
|June 4, 2010
PubMed
Summary

Beta-2 adrenoceptor (ADRB2) gene variations influence systemic vascular resistance (SVR) responses to terbutaline. Individuals with Gly16 showed greater vasodilatation compared to Arg16 during ganglionic blockade, suggesting augmented ADRB2 function.

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Area of Science:

  • Pharmacogenomics
  • Cardiovascular Physiology
  • Molecular Biology

Background:

  • Beta-2 adrenoceptor (ADRB2) gene polymorphisms, specifically at SNP positions 16 and 27, are known to influence vascular responses.
  • Previous studies on regional infusions showed greater vasodilatation with Gly16 homozygotes, while systemic infusions yielded conflicting results, possibly due to baroreflexes.

Purpose of the Study:

  • To investigate the hypothesis that ADRB2 gene variation influences systemic vascular resistance (SVR) response to the ADRB2 agonist terbutaline (Terb) during ganglionic blockade.
  • To elucidate the role of specific ADRB2 haplotypes (Arg16 + Gln27, Gly16 + Gln27, Gly16 + Glu27) in cardiovascular responses.

Main Methods:

  • Recruited 40 healthy adults genotyped for ADRB2 haplotypes.
  • Administered terbutaline intravenously during ganglionic blockade induced by trimethaphan and maintained blood pressure with phenylephrine.
  • Measured arterial pressure and cardiac output, and analyzed lymphocyte ADRB2 density and binding conformation ex vivo.

Main Results:

  • A trend for haplotype to affect SVR change was observed (P = 0.06).
  • At the highest terbutaline dose, Gly16 homozygotes exhibited significantly lower SVR compared to Arg16 homozygotes (P = 0.03).
  • Lymphocyte ADRB2 receptor density was higher in Gly16 compared to Arg16 individuals (P = 0.05).

Conclusions:

  • ADRB2 gene variation, particularly the Gly16 polymorphism, influences systemic vascular resistance response to terbutaline during ganglionic blockade.
  • Findings suggest augmented ADRB2 function in Gly16 + Glu27 homozygotes, supporting the role of ADRB2 gene variation in modulating vasodilatation.