THROMBIN REGULATES NERVE GROWTH-FACTOR SECRETION FROM VASCULAR, BUT NOT BLADDER SMOOTH-MUSCLE CELLS

The production of nerve growth factor (NGF) in peripheral organs may p lay a role in the pathophysiology of hypertension and in obstructive d isorders of the bladder outlet. We have been examining the cellular pr ocesses of NGF delivery and secretion in smooth muscle. NGF secretion from vascular smooth muscle cells (VSMCs) cultured from genetically hy pertensive (WKHT), hyperactive (WKHA), and a control Wistar rat strain were assayed using a two-site ELISA of the culture media. Bladder smo oth muscle cells (BSMCs) from the Wistar strain were also studied. The serine protease, thrombin, increased NGF secretion from all types of VSMCs but had no effect on Wistar BSMCs. The thrombin-mediated increas e in NGF secretion was prevented by actinomycin D and cycloheximide, s uggesting that RNA transcription and protein synthesis are required. T he effect of thrombin was additive with a phorbol ester-induced elevat ion in NGF secretion rates from 4 to 6 h and was attenuated by a 24-h downregulation of protein kinase C. These results suggest that extrace llular protease activity may regulate NGF secretion in smooth muscle. Thrombin may act in response to vascular injury, increasing NGF secret ion from VSMCs, initiating VSMC migration, and preparing the VSMCs for reinnervation following an insult.