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

• Published in: Journal of vascular surgery 1995-05, Vol.21 (5), p.792-800
• Main Authors: Moursi, Mohammed M., Beebe, Hugh G., Messina, Louis M., Welling, Theodore H., Stanley, James C.
• Format: Article
• Language: English
• Subjects: 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
• ISSN: 0741-5214; 1097-6809
• DOI: 10.1016/S0741-5214(05)80010-2

Purpose: This study was designed to define the effects of β-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 β-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, β blockade reduced the aortic arch diameter in blotchy mice to 0.11±0.03 cm. Mean heart rate in group III β-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/μg protein) noted in group I normal mice (5.82±1.06 cpm/μg protein). Aortic LO activity in group III blotchy mice remained low (2.09±0.85 cpm/μg protein) despite administration of β-blockers. Conclusions: This is the first study to document an actual decrease in the level of aortic LO activity in blotchy mouse. β-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.