Cellular distribution of immunoreactive urotensin-II in human tissues with evidence of increased expression in atherosclerosis and a greater constrictor response of small compared to large coronary arteries.
We detected urotensin-II-like immunoreactivity in the endothelium of normal human blood vessels from heart, kidney, placenta, adrenal, thyroid and umbilical cord. Immunoreactivity was also detected in endocardial endothelial and kidney epithelial cells. In atherosclerotic coronary artery, immunoreactivity localized to regions of macrophage infiltration. Urotensin-II constricted human atherosclerotic epicardial coronary arteries with pD2=10.58 +/- 0.46 (mean +/- S.E.M.) and Emax=11.4 +/- 4.2% KCl and small coronary arteries with pD2=9.25 +/- 0.38 and Emax=77 +/- 16% KCl. Small coronary arteries clearly exhibited a greater maximum response to urotensin-II than epicardial vessels. This enhanced responsiveness may be of importance in heart failure, where circulating concentrations of U-II are increased, or in atherosclerosis where focally up-regulated urotensin-II production may act down stream to produce significant vasospasm, compromising blood flow to the myocardium. We conclude that urotensin-II is a locally released vasoactive mediator that may be an important regulator of blood flow particularly to the myocardium and may have a specific role in human atherosclerosis.
Clinical Pharmacology Unit, University of Cambridge, Level 6 Centre for Clinical Investigation, Box 110, Addenbrooke's Hospital, Cambridge CB22QQ, UK. jjm1003@medschl.cam.ac.uk
Janet J
JJ
Maguire
Rhoda E
RE
Kuc
Katherine E
KE
Wiley
Matthias J
MJ
Kleinz
Anthony P
AP
Davenport
D001161:Arteriosclerosis / Q000503:physiopathology; D003327:Coronary Disease / Q000503:physiopathology; D003331:Coronary Vessels / Q000187:drug effects / Q000502:physiology*; D005786:Gene Expression Regulation; D006801:Humans; D014579:Urotensins / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*; D014662:Vasoconstrictor Agents
D014579:Urotensins; D014662:Vasoconstrictor Agents; C029677:urotensin II