INHIBITION OF AORTIC-ANEURYSM DEVELOPMENT IN BLOTCHY MICE BY BETA-ADRENERGIC-BLOCKADE INDEPENDENT OF ALTERED LYSYL OXIDASE ACTIVITY

Purpose: This study was designed to define the effects of beta-adrener gic blockade on aortic lysyl oxidase (LO), an enzyme responsible for e lastin and collagen cross-linking, and aneurysm formation in the blotc hy mouse. It was hypothesized that beta-blockade would inhibit the dev elopment of aneurysms because of its hemodynamic effect rather than a direct effect on LO activity. Methods: Three groups of mice were studi ed: group I-normal littermates of blotchy mice; group II-untreated blo tchy 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 analys is. The study was concluded when the mice were 4 months of age. At tha t time systolic blood pressure, heart rate, and aortic diameters were measured, and the entire aorta from each mouse was subjected to a bioa ssay 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 a rch 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 un treated 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/mu g protein) noted in group I normal mice (5.82 +/- 1.06 cpm/mu g protein). Aortic LO activity in group III blo tchy mice remained low (2.09 +/- 0.85 cpm/mu g protein) despite admini stration of beta-blockers. Conclusions: This is the first study to doc ument an actual decrease in the level of aortic LO activity in blotchy mouse. beta-Blockade inhibits development of aortic aneurysms in blot chy mice. This is associated with a reduction in heart rate, but not b y alterations in LO activity.