Altered regulation of nerve growth factor secretion by cultured vascular smooth muscle cells from hypertensive rats. Spitsbergen, John M., Jeanine S. Stewart, and Jeremy B. Tuttle. Departments of Urology and Neuroscience, University of Virginia School of Medicine, Charlottesville, VA 22908
APStracts 2:0180H, 1995.
Vascular tissues from spontaneously hypertensive rats (SHR) exhibit increased nerve growth factor (NGF) levels and increased density of sympathetic innervation compared to those from normotensive Wistar -Kyoto (WKY) rats. The present study asked whether basal NGF secretion or secretion elicited by agents analogous to sympathetic neurotransmitters differs in cultured vascular smooth muscle cells (VSMCs) from SHR and WKY rats. VSMCs were maintained in serum free medium (SFM) for 72 hr, then treated and sampled at 4, 6, 8 and 24 hr. Conditioned medium was assayed for NGF using a two-site enzyme -linked immunoassay. NGF secretion by SHR (19.2+/-4.6 pg/well/48 hr) and WKY VSMCs (16.7+/-5.4 pg/well/48 hr) was similar in cultures grown in serum containing medium, while SHR VSMCs maintained in SFM secrete more NGF than WKY VSMCs (9.1+/-1.9 vs 2.9+/-0.4 pg/well/24 hr, respectively). Treatment of cultures with phenylephrine (PE, 0.1 -10 NM), neuropeptide-Y (NPY, 1 to 1000 nM) or [alpha],[beta] -methyleneadenosine 5'-triphosphate ([alpha][beta]MATP, 10 and 100 NM) had no effect on NGF secretion by WKY VSMCs, while increasing NGF secretion by SHR VSMCs. Treatment with isoproterenol (ISO, 0.1-10 NM) decreased NGF secretion by WKY VSMCs but not SHR VSMCs. These data indicate that the regulation of NGF secretion by sympathetic neurotransmitter receptors is different for cultured VSMCs from SHR and WKY rats. If similar differences exist in vivo, they could account for the alterations in NGF levels and sympathetic innervation which are observed. 

Received 27 September 1994; accepted in final form 7 March 1995.
APS Manuscript Number H868-4.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on  9 May 1995.