title: Stretch-activated signaling of nerve growth factor secretion in bladder and vascular smooth muscle cells from hypertensive and hyperactive rats.
abstract: Elevated vascular (VSMC) and bladder smooth muscle (BSMC) NGF are associated with altered visceral innervation in the spontaneously hypertensive rat (SHR: hypertensive, behaviorally hyperactive) compared with control Wistar-Kyotos (WKYs). Stretch stimulates increased NGF production in BSMCs. To elucidate whether stretch induces NGF synthesis in VSMCs, and to determine if disturbances in stretch-mediated NGF production contribute to the elevated tissue levels of NGF in SHRs, we subjected VSMCs and BSMCs cultured from four established inbred rat strains (WKY, WKHA: hyperactive; SHR and WKHT: hypertensive) to several stretch paradigms. For VSMCs, acute and cyclic stretch affected cells derived from hypertensive rats (80-100% increase over control) but not from normotensive strains. For BSMCs, cyclic and static stretch increased NGF secretion in all four strains, but had a two- to threefold greater effect in cells from SHRs and WKHTs (increase up to 600%) at early time points. At later time points of a 24-h experimental period, stretch increased NGF output up to 400% in SHR and WKHA cultures. Thus, defects that influence early induction of stretch-mediated SHR NGF secretion cosegregate with the hypertensive phenotype. Stretch-gated ion channel inhibitors, voltage-gated ion channel inhibitors, and protease inhibitors failed to affect stretch-induced BSMC NGF secretion. In contrast, gene transcription, intracellular calcium, protein kinase C (PKC), and autocrine release of an unknown factor may play a role in the elevated NGF secretion observed in smooth muscle from hypertensive animals. Altered stretch-induced smooth muscle NGF secretion may contribute to the augmented vascular and bladder NGF content associated with high blood pressure and hyperactive voiding in SHRs.
authors.affiliation: Department of Neuroscience, University of Virginia School of Medicine, Charlottesville, Virginia 22908, USA.
authors.forename: D B
authors.initials: DB
authors.lastname: Clemow
authors.forename: W D
authors.initials: WD
authors.lastname: Steers
authors.forename: J B
authors.initials: JB
authors.lastname: Tuttle
mesh_terms: D000818:Animals; D001013:Aorta, Thoracic / Q000502:physiology / Q000503:physiopathology; D001289:Attention Deficit Disorder with Hyperactivity / Q000503:physiopathology; D002478:Cells, Cultured; D006973:Hypertension / Q000503:physiopathology*; D009130:Muscle, Smooth / Q000502:physiology / Q000503:physiopathology*; D009131:Muscle, Smooth, Vascular / Q000502:physiology / Q000503:physiopathology*; D009414:Nerve Growth Factors / Q000235:genetics* / Q000378:metabolism*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D015398:Signal Transduction; D013314:Stress, Mechanical; D014158:Transcription, Genetic; D001743:Urinary Bladder / Q000502:physiology / Q000503:physiopathology*
chemical_list: D009414:Nerve Growth Factors