Inhibition of aortic aneurysm development in blotchy mice by beta adrenergic blockade independent of altered lysyl oxidase activity

J Vasc Surg. 1995 May;21(5):792-9; discussion 799-800. doi: 10.1016/s0741-5214(05)80010-2.

Abstract

Purpose: This study was designed to define the effects of beta-adrenergic blockade on aortic lysyl oxidase (LO), an enzyme responsible for elastin and collagen cross-linking, and aneurysm formation in the blotchy mouse. It was hypothesized that beta-blockade would inhibit the development of aneurysms because of its hemodynamic effect rather than a direct effect on LO activity.

Methods: Three groups of mice were studied: group I--normal littermates of blotchy mice; group II--untreated blotchy mice; group III--blotchy mice given either propranolol, atenolol, or nadolol. Data from the three different beta blocker-treated animals, group III, were statistically identical and were combined for analysis. The study was concluded when the mice were 4 months of age. At that time systolic blood pressure, heart rate, and aortic diameters were measured, and the entire aorta from each mouse was subjected to a bioassay for LO activity.

Results: Group I normal mice had an aortic arch diameter of 0.10 +/- 0.02 cm. Group II blotchy mice developed aortic arch aneurysms with a diameter of 0.21 +/- 0.03 cm. In Group III, beta blockade reduced the aortic arch diameter in blotchy mice to 0.11 +/- 0.03 cm. Mean heart rate in group III beta-blocked mice was reduced 25% compared with group I normal mice, and 18% compared with group II untreated blotchy mice. Blood pressures were similar in all three groups. Group II blotchy mice exhibited approximately half of the aortic LO activity (2.43 +/- 0.57 cpm/micrograms protein) noted in group I normal mice (5.82 +/- 1.06 cpm/micrograms protein). Aortic LO activity in group III blotchy mice remained low (2.09 +/- 0.85 cpm/micrograms protein) despite administration of beta-blockers.

Conclusions: This is the first study to document an actual decrease in the level of aortic LO activity in blotchy mouse. beta-Blockade inhibits development of aortic aneurysms in blotchy mice. This is associated with a reduction in heart rate, but not by alterations in LO activity.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Aorta, Thoracic / drug effects
  • Aorta, Thoracic / pathology
  • Aortic Aneurysm / enzymology
  • Aortic Aneurysm / pathology
  • Aortic Aneurysm / physiopathology*
  • Aortic Aneurysm / prevention & control
  • Atenolol / pharmacology*
  • Atenolol / therapeutic use
  • Blood Pressure / drug effects
  • Heart Rate / drug effects
  • Male
  • Mice
  • Mice, Mutant Strains
  • Nadolol / pharmacology*
  • Nadolol / therapeutic use
  • Propranolol / pharmacology*
  • Propranolol / therapeutic use
  • Protein-Lysine 6-Oxidase / drug effects*
  • Protein-Lysine 6-Oxidase / metabolism

Substances

  • Nadolol
  • Atenolol
  • Propranolol
  • Protein-Lysine 6-Oxidase