INCREASED NERVE GROWTH-FACTOR MESSENGER-RNA STABILITY MAY UNDERLIE ELEVATED NERVE GROWTH-FACTOR SECRETION FROM HYPERTENSIVE VASCULAR SMOOTH-MUSCLE CELLS

Altered nerve growth factor (NGF) regulation has been linked to the pa thophysiology of hypertension. Vascular smooth muscle cells from an in bred hypertensive, but normoactive rat strain (WKHT) secreted NGF at a greater rate than from a hyperactive, normotensive strain (WKHA). Exp osure to phorbol ester increased NGF secretion rates from WKHT by 400- 800% but not from WKHA vascular muscle. NGF secretion rates from both WKHT and WKHA vascular cells were elevated by co-application of platel et-derived growth factor (PDGF) and transforming growth factor-beta 1 (TGF-beta 1) by 300-1000%. This response was partially attenuated by a ctinomycin D, an inhibitor of RNA transcription. These results suggest that regulation of NGF production does not occur solely at the level of transcription and post-transcriptional mechanisms operate. Analysis of NGF mRNA stability in the two strains following PDGF and TGF-beta 1 treatment showed that NGF mRNA in WKHT had a half-life of 126.2 +/- 11.68 min while in WKHA vascular smooth muscle cells, the half-life wa s 47.33 +/- 11.98 min. In addition to increased NGF mRNA stability in WKHT vascular muscle, these cells have an increased translational effi ciency of NGF protein; elevated synthesis of NGF protein per unit NGF mRNA. Differences in signaling pathways may result in increased NGF mR NA stability and translational efficiency that may account for the ele vated NGF protein in WKHT vascular smooth muscle cells. (C) 1998 Elsev ier Science B.V. All rights reserved.