Inhibition of aortic aneurysm development in blotchy mice by beta adrenergic blockade independent of altered lysyl oxidase activity.
OBJECTIVE
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.
Moursi
M M
MM
Department of Surgery, University of Michigan School of Medicine, Ann Arbor, USA.
Beebe
H G
HG
Messina
L M
LM
Welling
T H
TH
Stanley
J C
JC
D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000473:pathology; D001014:Aortic Aneurysm / Q000201:enzymology / Q000473:pathology / Q000503:physiopathology* / Q000517:prevention & control; D001262:Atenolol / Q000494:pharmacology* / Q000627:therapeutic use; D001794:Blood Pressure / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D009248:Nadolol / Q000494:pharmacology* / Q000627:therapeutic use; D011433:Propranolol / Q000494:pharmacology* / Q000627:therapeutic use; D008249:Protein-Lysine 6-Oxidase / Q000187:drug effects* / Q000378:metabolism
D009248:Nadolol; D001262:Atenolol; D011433:Propranolol; D008249:Protein-Lysine 6-Oxidase