title: Mitogen-activated protein kinase activity regulation role of angiotensin and endothelin systems in vascular smooth muscle cells.
abstract: To examine whether angiotensin II and endothelins produced in vascular smooth muscle cells can play roles in the regulation of mitogen-activated protein (MAP) kinase activity in vascular smooth muscle cells, we measured the activity of MAP kinases in cultured vascular smooth muscle cells, and determined effects of renin-angiotensin and endothelin systems activators and inhibitors. Angiotensin II and endothelin-1 produced an activation of MAP kinase activity in vascular smooth muscle cells, whereas the angiotensin receptor antagonist, losartan and the endothelin receptor antagonist, cyclo (D-alpha-aspartyl-L-prolyl-D-valyl-L-leucyl-D-tryptophyl, BQ123) inhibited the enzyme activity. MAP kinase activity in vascular smooth muscle cells was also inhibited either by the renin inhibitor pepstatin A or by the angiotensin-converting enzyme inhibitor captopril. The degree of the inhibition of MAP kinase activity by pepstatin A, captopril and losartan was almost the same. Renin produced a considerable increase in MAP kinase activity and the renin-induced MAP kinase activation was inhibited by pepstatin A. The endothelin precursor big endothelin-1 produced an increase of MAP kinase activity in vascular smooth muscle cells, whereas the endothelin-converting enzyme inhibitor phosphoramidon inhibited the enzyme activity. These findings suggest that functional renin-angiotensin system and endothelin system are present in vascular smooth muscle cells and these systems tonically serve to increase MAP kinase activity. It appears that renin or renin-like substances play the determining role in the regulation of renin-angiotensin system in vascular smooth muscle cells.
authors.affiliation: Department of Pharmacology, Showa Pharmaceutical University, Tokyo 194-8543, Machida, Japan. kubo@ac.shoyaku.ac.jp
authors.forename: T
authors.initials: T
authors.lastname: Kubo
authors.forename: T
authors.initials: T
authors.lastname: Ibusuki
authors.forename: S
authors.initials: S
authors.lastname: Chiba
authors.forename: T
authors.initials: T
authors.lastname: Kambe
authors.forename: R
authors.initials: R
authors.lastname: Fukumori
mesh_terms: D000803:Angiotensin I / Q000494:pharmacology; D000804:Angiotensin II / Q000494:pharmacology / Q000502:physiology*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D002216:Captopril / Q000494:pharmacology; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1 / Q000494:pharmacology; D016232:Endothelins / Q000494:pharmacology / Q000502:physiology*; D006020:Glycopeptides / Q000494:pharmacology; D019808:Losartan / Q000494:pharmacology; D008297:Male; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D010436:Pepstatins / Q000494:pharmacology; D010456:Peptides, Cyclic / Q000494:pharmacology; D011480:Protease Inhibitors / Q000494:pharmacology; D011498:Protein Precursors / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012083:Renin / Q000494:pharmacology
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1; D016232:Endothelins; D006020:Glycopeptides; D010436:Pepstatins; D010456:Peptides, Cyclic; D011480:Protease Inhibitors; D011498:Protein Precursors; C014195:Streptomyces pepsin inhibitor; D000804:Angiotensin II; D000803:Angiotensin I; D002216:Captopril; D020928:Mitogen-Activated Protein Kinases; D012083:Renin; D019808:Losartan; C072247:cyclo(Trp-Asp-Pro-Val-Leu); C008890:phosphoramidon; C031375:pepstatin