Pressure-induced connective tissue synthesis in pulmonary artery segments is dependent on intact endothelium.
Physiologic stimuli of connective tissue accumulation in pulmonary vascular remodeling are poorly defined. We postulated that increased pressure within central pulmonary arteries is a stimulus for connective tissue synthesis and the response is dependent on an intact endothelium. Mechanical tension equivalent to 50 mmHg pressure was applied for 4 h to isolated rat main pulmonary arteries (endothelium intact or removed), and incorporation of [14C]proline into collagen, [14C]valine into elastin, [3H]thymidine into DNA and pro alpha 1 (I) collagen mRNA levels were measured. In intact vessels, tension induced synthesis of collagen (3.1 +/- 0.4 vs. 2.3 +/- 0.5 [SEM] dpm X 10(2) [14C]-hydroxyproline/[mg protein.h]) (n = 10) and elastin (6.1 +/- 2.4 vs. 2.9 +/- 0.4 dpm X 10(3) [14C]valine/[mg protein.h]) (n = 5) (both P less than 0.05). Steady state mRNA levels of pro alpha 1 (I) collagen were also increased by tension (46 vs. 30 X 10(2) dpm hybridized/100 ng total RNA). However, the stimulus did not increase [3H]thymidine incorporation into DNA. In denuded vessels, tension had no effect on connective tissue synthesis or mRNA level of pro alpha 1 (I) collagen. Messenger RNA levels for v-sis were induced by tension in intact but not denuded vessels. Our findings establish that induction of vascular connective tissue synthesis by mechanical tension is dependent on an intact endothelium.
Tozzi
C A
CA
Department of Medicine, University of Medicine and Dentistry of New Jersey, New Brunswick 08903-0019.
Poiani
G J
GJ
Harangozo
A M
AM
Boyd
C D
CD
Riley
D J
DJ
D000199:Actins / Q000302:isolation & purification; D000818:Animals; D001794:Blood Pressure; D015152:Blotting, Northern; D003094:Collagen / Q000096:biosynthesis / Q000302:isolation & purification; D003238:Connective Tissue / Q000378:metabolism / Q000502:physiology*; D004549:Elastin / Q000096:biosynthesis; D004730:Endothelium, Vascular / Q000201:enzymology / Q000502:physiology* / Q000648:ultrastructure; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008297:Male; D008855:Microscopy, Electron, Scanning; D009126:Muscle Relaxation; D010982:Platelet-Derived Growth Factor / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D020574:Proto-Oncogene Proteins c-sis; D011651:Pulmonary Artery / Q000378:metabolism / Q000502:physiology*; D012333:RNA, Messenger / Q000302:isolation & purification; D051381:Rats; D013936:Thymidine / Q000378:metabolism
D000199:Actins; D010982:Platelet-Derived Growth Factor; D011518:Proto-Oncogene Proteins; D020574:Proto-Oncogene Proteins c-sis; D012333:RNA, Messenger; D003094:Collagen; D004549:Elastin; D007770:L-Lactate Dehydrogenase; D013936:Thymidine