ALTERED REGULATION OF NERVE GROWTH-FACTOR SECRETION BY CULTURED VSMCSFROM HYPERTENSIVE RATS

Vascular tissues from spontaneously hypertensive rats (SHR) exhibit in creased nerve growth factor (NGF) levels and increased density of symp athetic innervation compared with those from normotensive Wistar-Kyoto (WKY) rats. The present study asked whether basal NGF secretion or se cretion elicited by agents analogous to sympathetic neurotransmitters differ in cultured vascular smooth muscle cells (VSMCs) from SHR and W KY rats. VSMCs were maintained in serum-free medium (SFM) for 72 h and then treated and sampled at 4, 6, 8, and 24 h. Conditioned medium was assayed for NGF using a two-site enzyme-linked immunoassay. NGF secre tion by SHR (19.2 +/- 4.6 pg . well(-1). 48 h(-1)) and WKY VSMCs (16.7 +/- 5.4 pg . well(-1). 48 h(-1)) was similar in cultures grown in ser um-containing medium, whereas SHR VSMCs maintained in SFM secrete more NGF than WKY VSMCs (9.1 +/- 1.9 vs. 2.9 +/- 0.4 pg . well(-1). 24 h(- 1), respectively). Treatment of cultures with phenylephrine (0.1-10 mu M), neuropeptide Y (1-1,000 nM), or alpha,beta-methyleneadenosine 5'- triphosphate (10 and 100 mu M) had no effect on NGF secretion by WKY V SMCs, while increasing NGF secretion by SHR VSMCs. Treatment with isop roterenol (0.1-10 mu M) decreased NGF secretion by WKY VSMCs but not S HR 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 cou ld account for the alterations in NGF levels and sympathetic innervati on that are observed.