Increased perfusion pressure enhances the expression of endothelin (ETB) and angiotensin II (AT1, AT2) receptors in rat mesenteric artery smooth muscle cells.
In the present study, we hypothesized that changes in perfusion pressure result in altered expression of mRNA and protein encoding for the ETA-, ETB-, AT1- and AT2-receptors in rat mesenteric vessels. Segments of the rat mesenteric artery were cannulated with glass micropipettes, pressurized and luminally perfused in a perfusion chamber. After either exposure to no ("organ culture" (0 mmHg)), normal (85/75 mmHg) or high pressure (160/150 mmHg) at constant flow for 1-17 h, the vessel segments were snap frozen and real-time polymerase chain reaction was performed to quantify the ET- and AT-receptor mRNA content, or immersed in a fixative solution, dehydrated, frozen, cut in a cryostat and immunohistology stained for ET- and AT-receptor protein. The mRNA expressions of ETB and of AT2 were significantly enhanced in vessels exposed to high perfusion pressure, compared with normal and no perfusion pressure at 4 h. In concordance, AT1-, AT2- and ETB-receptor proteins were up-regulated at 17 h of high perfusion pressure. In conclusion, the results from our rat perfusion model suggest a more important role of shear stress than pure pressure alone and may serve as a surrogate model for studies designed to investigate hypertension mechanisms.
Division of Experimental Vascular Research, Institute of Clinical Science in Lund, Lund University, Lund, Sweden. isaklindstedt@hotmail.com
Isak
I
Lindstedt
Cang-Bao
CB
Xu
Yaping
Y
Zhang
Lars
L
Edvinsson
D000818:Animals; D001794:Blood Pressure / Q000502:physiology*; D005786:Gene Expression Regulation / Q000502:physiology*; D008638:Mesenteric Arteries / Q000378:metabolism / Q000502:physiology*; D032389:Myocytes, Smooth Muscle / Q000378:metabolism*; D010477:Perfusion; D011673:Pulsatile Flow / Q000502:physiology*; D020871:RNA Stability; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D044140:Receptor, Angiotensin, Type 1 / Q000096:biosynthesis* / Q000235:genetics; D044139:Receptor, Angiotensin, Type 2 / Q000096:biosynthesis* / Q000235:genetics; D044022:Receptor, Endothelin A / Q000096:biosynthesis* / Q000235:genetics; D044023:Receptor, Endothelin B / Q000096:biosynthesis* / Q000235:genetics
D012333:RNA, Messenger; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B