Contribution of Nerve Growth Factor to The Increased Sympathetic Nerve Activity in Hypertension

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Increased sympathetic nervous activity has been demonstrated in spontaneously hypertensive rats(SHR) and human essential hypertension. Especially, in SHR, increased sympathetic nerve innervation and enhanced norepinephrine(NE) release from vascular tissue have been reported, precise mechanisms of which are not clearly known. To elucidate the contribution of Nerve growth factor(NGF) to the increased sympathetic nervous activity in SHR, the secretion of NGF from cultured vascular smooth muscle cells(VSMCs) was examined and NGF content in various tissues from SHR and control Wistar-Kyoto rats(WKY) was measured. The effects of NGF on NE release from the sympathetic nerve endings were also examined. NGF was purified from mouse submandibular gland according to the Bocchini's method. VSMCs were obtained from the aorta of WKY by explant method. NGF activity was measured by bioassay and NGF content was measured by enzyme immunoassay. Effects of NGF on NE overflow to electrical stimulation were examined using perfused mesenteric artery preparation. 1) Conditioned medium prepared from VSMCs had neurite extention effects on sensory and sympathetic neurons and this effect was blocked by anti-NGF serum. 2) At 3 weeks of age, SHR had a greater NGF content in the spleen, the sciatic nerve, and the mesenteric artery in comparison with WKY.However, these differences were not observed in the adults animals. 3) The expression of NGFmRNA was increased in media of mesenteric artery in in situ hybridization. 4) NGF secretion from cultured VSMCs and mesenteric artery and aorta segment was not significantly difference in in situ hybridization. 5) NGF inhibited NE overflow to electrical stimulation from sympathetic nerve endings in a dose-dependent manner. Inhibition of NE overflow also occurred in the presence of a neuronal uptake blocker, desipramine(5x10-8M). 6) Neuromodulatory effect of NGF was attenuated in 4 week old SHR.However, there were no significant differences between 12 week o