PROPRANOLOL-INDUCED ELEVATION OF PULMONARY COLLAGEN

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Abstract
Current concepts of collagen metabolism suggest that fibroblasts tightly control collagen production. One of the possible mechanisms of control is via the cyclic nucleotides, cAMP and cGMP. .beta. adrenergic agonists, by elevating intracellular cAMP levels, in vitro suppressed fibroblast collagen production; whereas .beta. adrenergic antagonists were effective in removing this suppression by blocking the rise in cAMP. Study with mice showed that administration of the .beta.-adrenergic antagonist, propranolol, at a dose demonstrated to decrease the ratio of cAMP to cGMP, resulted in an elevation in total lung collagen in vivo. The increase in collagen was evident only when propranolol was administered before and during acute lung damage induced by either butylated hydroxytoluene, bleomycin or high concentrations of O2. There was no increase in lung collagen when propranolol administration was delayed after injury or when given to an undamaged lung. Via .beta. adrenergic blockade by propranolol, fibroblasts involved in the normal reparative process may have lost a mechanism for regulatory control, resulting in excessive deposition of collagen.