title: Cyclic stretch induces vascular smooth muscle cell alignment via NO signaling.
abstract: We investigated the effects of cyclic stretch on vascular smooth muscle cell (VSMC) alignment and potential overlap of signaling modalities with stretch-induced proliferation. VSMC were subjected to graded stretch (1 Hz at 100-124% of resting length) for 48 h. Graded stretch resulted in graded VSMC alignment from a minimum of completely random orientation to a maximum of ~80-85 degrees to the stretch vector. Alignment was reversible within 48 h of stretch cessation and independent of signaling modalities mediating stretch-induced proliferation: modulation of IGF-1, MAPK, phosphatidylinositol 3-kinase, tyrosine kinase, and stretch-activated calcium channels did not affect alignment. Nitric oxide (NO) synthase (NOS) blockade uncoupled alignment. Neither the NO donor, cytokine-induced NOS activity, nor L-citrulline affected alignment, but inhibited VSMC proliferation. Therefore, stretch-induced proliferation and alignment are differentially regulated, with NO a common signaling molecule for both. Targeting NOS in states such as restenosis and hypertension may prove to be beneficial.
authors.affiliation: Department of Physiology, Midwestern University, 19555 N. 59th Avenue, Glendale, AZ 85308, USA. pstand@arizona.midwestern.edu
authors.forename: Paul R
authors.initials: PR
authors.lastname: Standley
authors.forename: Antonino
authors.initials: A
authors.lastname: Cammarata
authors.forename: Brian P
authors.initials: BP
authors.lastname: Nolan
authors.forename: Christian T
authors.initials: CT
authors.lastname: Purgason
authors.forename: Melinda A
authors.initials: MA
authors.lastname: Stanley
authors.forename: Antonino
authors.initials: A
authors.lastname: Camaratta
mesh_terms: D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D001011:Aorta / Q000166:cytology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000378:metabolism; D002455:Cell Division; D002470:Cell Survival; D002478:Cells, Cultured; D016207:Cytokines / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D066298:In Vitro Techniques; D007334:Insulin-Like Growth Factor I / Q000037:antagonists & inhibitors / Q000276:immunology; D032342:Muscle Cells / Q000502:physiology*; D009119:Muscle Contraction / Q000502:physiology*; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000502:physiology*; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D051381:Rats; D011919:Rats, Inbred Strains; D015398:Signal Transduction / Q000502:physiology*; D013314:Stress, Mechanical; D019323:omega-N-Methylarginine / Q000494:pharmacology
chemical_list: D000906:Antibodies; D002121:Calcium Channel Blockers; D015220:Calcium Channels; D016207:Cytokines; D004791:Enzyme Inhibitors; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D007334:Insulin-Like Growth Factor I; D019001:Nitric Oxide Synthase