title: Effect of cyclic axial stretch of rat arteries on endothelial cytoskeletal morphology and vascular reactivity.
abstract: Pulsatile fluid shear stress and circumferential stretch are responsible for the axial alignment of vascular endothelial cells and their actin stress fibers in vivo. We studied the effect of cyclic alterations in axial stretch independent of flow on endothelial cytoskeletal organization in intact arteries and determined if functional alterations accompanied morphologic alterations. Rat renal arteries were axially stretched (20%, 0.5 Hz) around their in vivo lengths, for up to 4h. Actin stress fibers were examined by immunofluorescent staining. We found that cyclic axial stretching of intact vessels under normal transmural pressure in the absence of shear stress induces within a few hours realignment of endothelial actin stress fibers toward the circumferential direction. Concomitant with this morphologic alteration, the sensitivity (log(EC(50))) to the endothelium-dependent vasodilator (acetylcholine) was significantly decreased in the stretched vessels (after stretching -5.15+/-0.79 and before stretching -6.71+/-0.78, resp.), while there was no difference in sodium nitroprusside (SNP) sensitivity. There was no difference in sensitivity to both acetylcholine and SNP in time control vessels. Similar to cultured cells, endothelial cells in intact vessels subjected to cyclic stretching reorganize their actin filaments almost perpendicular to the stretching direction. Accompanying this morphological alteration is a loss of endothelium-dependent vasodilation but not of smooth muscle responsiveness.
authors.affiliation: Laboratory for Physiology, Institute for Cardiovascular Research-VU, Vrije University, Van der Boechorststraat 7, 1081 BT Amsterdam, The Netherlands. sipkema@physiol.med.vu.nl
authors.forename: Pieter
authors.initials: P
authors.lastname: Sipkema
authors.forename: Peter J W
authors.initials: PJ
authors.lastname: van der Linden
authors.forename: Nico
authors.initials: N
authors.lastname: Westerhof
authors.forename: Frank C P
authors.initials: FC
authors.lastname: Yin
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000199:Actins / Q000502:physiology* / Q000648:ultrastructure*; D000818:Animals; D001794:Blood Pressure / Q000502:physiology; D016764:Cell Polarity / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D003599:Cytoskeleton / Q000187:drug effects / Q000502:physiology / Q000648:ultrastructure; D004730:Endothelium, Vascular / Q000166:cytology* / Q000187:drug effects / Q000502:physiology*; D040542:Mechanotransduction, Cellular / Q000502:physiology; D008846:Micromanipulation / Q000379:methods; D008863:Microspheres; D009038:Motion; D009599:Nitroprusside / Q000494:pharmacology; D010507:Periodicity; D010812:Physical Stimulation / Q000379:methods; D010865:Pilot Projects; D017534:Radial Artery / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D051381:Rats; D012016:Reference Values; D013314:Stress, Mechanical; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology
chemical_list: D000199:Actins; D009599:Nitroprusside; D000109:Acetylcholine