Cyclic stretch induces vascular smooth muscle cell alignment via NO signaling.
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.
Standley
Paul R
PR
Department of Physiology, Midwestern University, 19555 N. 59th Avenue, Glendale, AZ 85308, USA. pstand@arizona.midwestern.edu
Cammarata
Antonino
A
Nolan
Brian P
BP
Purgason
Christian T
CT
Stanley
Melinda A
MA
Camaratta
Antonino
A
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
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