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.
Department of Physiological Sciences, Lund University, Lund, Sweden.
A
A
Zeidan
I
I
Nordström
K
K
Dreja
U
U
Malmqvist
P
P
Hellstrand
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