Nerve growth factor synthesis in vascular smooth muscle.

Abstract

Details of the interdependent, trophic relation between smooth muscle and its neural innervation are not well known despite suggestions that neural influences may contribute significantly to hypertensive and other cardiovascular disease. Vascular smooth muscle is a major target of innervation by neurons of the sympathetic nervous system. Sympathetic neurons depend on a constant supply of the potent neurotrophic peptide nerve growth factor. Nerve growth factor regulates an impressive list of neuronal and perhaps muscle properties, yet its source in vessels and the determinants of its synthesis are not known. We have taken advantage of the cytoarchitecture of the aorta to demonstrate that vascular smooth muscle cells synthesize nerve growth factor. The survival of cultured sympathetic neurons is supported in a nerve growth factor-dependent manner by co-culture with pure rat aortic vascular smooth muscle cells. Furthermore, pure smooth muscle cell cultures contain nerve growth factorspecific messenger RNA. Levels of messenger nucleic acid coding for nerve growth factor in smooth muscle are regulated by contractile agonists (angiotensin II, arginine vasopressin) and the adrenergic agonist phenylephrine. This suggests a link between muscle activity and growth factor production. Secretion of nerve growth factor protein by vascular smooth muscle was measured using a sensitive two-site immunoassay. Secretion is highest during muscle growth. Secretion is elevated by angiotensin II and arginine vasopression but slightly inhibited by phenylephrine. These results suggest that cultured vascular smooth muscle can serve as a useful model in which to study the cellular regulation of trophic factor synthesis in health and disease. (Hypertension 1991;18:730-741)

Persistent Reduction in Renal Nerve Growth Factor mRNA After Perindopril Treatment of Young Spontaneously Hypertensive Rats

“…The relative abundance of NGF mRNA in young SHR was increased by angiotensin infusion and decreased by ACE inhibition. These findings extend previous results in other studies in which exogenous angiotensin increases NGF production, 11,12 whereas AT 1 angiotensin receptor antagonism decreases NGF levels. 13 The most interesting observation was that brief treatment with perindopril was followed by a persistent and significant reduction in renal NGF mRNA.…”

“…10 In addition, angiotensin may modulate sympathetic innervation by effects on NGF in key tissues. Angiotensin increases the secretion of NGF from vascular smooth muscle cells in vitro, 11,12 and Ang II receptor blockade reduces tissue levels of NGF. 13 In most tissues, including the kidney, the density of sympathetic innervation correlates closely with tissues levels of NGF peptide 14 and mRNA, 15 both of which are intercorrelated in target tissues.…”

The spontaneously hypertensive rat: insight into the pathogenesis of irritative symptoms in benign prostatic hyperplasia and young anxious males

“…It is synthesized in smooth muscle (Creedon & Tuttle, 1991) and taken up by innervating neurons that express NGF receptors. NGF specifies the form and size of the innervating nerves and affects neurotransmission at sympathetic junctions.…”

“…Vascular smooth muscle cells (VSMCs) in culture secrete NGF, as assayed by sympathetic neuronal survival and via a two-site immunoassay (ELISA) (Creedon & Tuttle, 1991;Ueyama et al 1993). VSMCs derived from SHR aorta, and bladder smooth muscle cells (BDSM) secrete more NGF than WKY (Clemow et al 1996).…”

“…Ambient levels of mRNA are first elevated by exposure to platelet-derived growth factor and transforming growth factor beta (Creedon & Tuttle, 1991). Further transcription is prevented by actinomycin D, and the rate of decay of the NGF mRNA levels measured concurrently with NGF protein secretion (Sherer et al 1998).…”