Propranolol stimulates the crosslinking of matrix components in skin from the aneurysm-prone blotchy mouse

Propranolol prevents or delays the formation of aortic aneurysms in both the lathyritic turkey and the Blotchy mouse models. This finding in the turkey is reported to be a direct effect on crosslinking of aortic collagen and elastin, independent of effects on pulse and blood pressure. The present work was performed to evaluate this hypothesis in the mouse model by studying the effect of propranolol on the insolubility of matrix proteins of skin, which would isolate the phenomenon from direct hemodynamic effects. Eight 6- to 8-week-old Blotchy mice were fed a diet containing 0.10% (w/w) propranolol for 12 weeks, and six Blotchy controls ate regular chow. At sacrifice the skins were extracted with 8 M urea, and the soluble and insoluble fractions were analyzed for hydroxyproline to determine the collagen contents. The elastin was estimated by subtracting the collagen from the insoluble fraction. There was a 147% increase in insoluble elastin with propranolol and a lesser increase of 54% in insoluble collagen. These results suggest that propranolol has a direct effect on crosslinking of matrix components.