Enhanced plasminogen activator activity in vascular cells treated with propranolol

Abstract

Propranolol, a β-blocker, increased plasminogen activator (PA) activity in confluent bovine aortic endothelial cells (BAEC) and rat smooth muscle cells (SMC). This effect was dose-dependent (10–100 μM) and time-dependent. Stimulation, occurring with both (−) and (+) isomers of propranolol, was detectable after 6 h and lasted at least 24 h of incubation with the drug. PA activity was determined after different times of incubation in cell extracts (0.25%, Triton X-100) and in serum free conditioned medium (CM) by amidolytic assay. In BAEC, PA activity increased both in cell extracts and CM, but only in cell extracts in rat SMC. Other β-blockers tested, like pindolol and metoprolol, were ineffective in our system. Fibrin autography of cell extracts and CM from BAEC showed a larger lysis zone corresponding to urokinase PA, while in rat SMC, the larger lysis zone corresponded to tissue-type PA. Neither active PAI-1 (amidolytic assay) nor its total amount (active plus latent), evaluated by reverse fibrin technique, were modified by propranolol treatment. This hitherto undescribed effect, although seen at relatively high doses, could be of relevance among the cardiovascular activities of propranolol.