Stretch-dependent modulation of contractility and growth in smooth muscle of rat portal vein.
Increased intraluminal pressure of the rat portal vein in vivo causes hypertrophy and altered contractility in 1 to 7 days. We have used organ cultures to investigate mechanisms involved in this adaptation to mechanical load. Strips of rat portal vein were cultured for 3 days, either undistended or loaded by a weight. Length-force relations were shifted toward longer length in stretched cultured veins compared with freshly dissected veins, whereas the length-force relations of unstretched cultured veins were shifted in the opposite direction. This occurred after culture either with or without 10% FCS to promote growth. The wet weight of loaded veins increased by 56% in the presence of FCS, whereas that of undistended control veins increased by 24%. No weight increase was seen in serum-free culture. The dry/wet weight ratio decreased during culture with FCS but was not affected by stretch. Electron microscopy revealed increased cell cross-sectional area in stretched relative to unstretched veins, and protein contents were greater, as were [(3)H]thymidine and [(3)H]leucine incorporation rates. Growth responses were associated with the activation of stretch-sensitive extracellular signal-regulated kinases 1 and 2 and were inhibited by herbimycin A and PD 98059, inhibitors of extracellular signal-regulated kinases 1 and 2. The results demonstrate that by culture of whole vascular tissue, smooth muscle cells are maintained in the contractile phenotype and respond to stretch with a physiological adaptation involving hypertrophy/hyperplasia and remodeling of the contractile system, similar to that in vivo. Mechanical stimulation and growth factors are both required for functionally significant growth.
Zeidan
A
A
Department of Physiological Sciences, Lund University, Lund, Sweden.
Nordström
I
I
Dreja
K
K
Malmqvist
U
U
Hellstrand
P
P
D000818:Animals; D016227:Benzoquinones; D002417:Cattle; D003470:Culture Media / Q000494:pharmacology; D016895:Culture Media, Serum-Free; D004261:DNA Replication; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D005312:Fetal Blood / Q000502:physiology; D005419:Flavonoids / Q000494:pharmacology; D006965:Hyperplasia; D006984:Hypertrophy; D047029:Lactams, Macrocyclic; D019950:Mitogen-Activated Protein Kinase 1 / Q000502:physiology; D048052:Mitogen-Activated Protein Kinase 3; D020929:Mitogen-Activated Protein Kinase Kinases / Q000037:antagonists & inhibitors; D020928:Mitogen-Activated Protein Kinases / Q000502:physiology; D009119:Muscle Contraction / Q000502:physiology*; D024510:Muscle Development; D009124:Muscle Proteins / Q000096:biosynthesis; D009131:Muscle, Smooth, Vascular / Q000254:growth & development / Q000378:metabolism / Q000502:physiology*; D018919:Neovascularization, Physiologic / Q000502:physiology*; D009924:Organ Culture Techniques; D009929:Organ Size / Q000187:drug effects; D010641:Phenotype; D011169:Portal Vein / Q000254:growth & development / Q000502:physiology*; D011809:Quinones / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017828:Rifabutin / Q000031:analogs & derivatives; D015398:Signal Transduction; D013314:Stress, Mechanical
D016227:Benzoquinones; D003470:Culture Media; D016895:Culture Media, Serum-Free; D004791:Enzyme Inhibitors; D005419:Flavonoids; D047029:Lactams, Macrocyclic; D009124:Muscle Proteins; D011809:Quinones; D017828:Rifabutin; C020754:herbimycin; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D020929:Mitogen-Activated Protein Kinase Kinases; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one