Mitogen-activated protein kinase contributes to elevated basal tone in aortic smooth muscle from hypertensive rats.
The role of mitogen-activated protein kinase (MAPK) in increased basal tone -spontaneous resistance in vascular muscle strips- was clarified in aortic smooth muscle from deoxycorticosterone acetate (DOCA)-salt hypertensive rats. The MAPK/extracellular signal-regulated protein kinase (ERK) kinase inhibitor, PD098059 (2'-amino-3'-methoxyflavone), significantly inhibited basal tone in a dose-dependent manner. The basal level of ERK1/2 activation was inhibited by PD098059 and was significantly greater in hypertensive rats than in sham-operated rats. In contrast, inhibition with PD098059 was not observed in sham-operated rats. GF109203X (2-[1-(3-dimethylaminopropyl)-1H-indol-3-yl]-3-(1H-indol-3-yl)maleimide), an inhibitor of protein kinase C (PKC), decreased both basal tone and ERK1/2 activity in the hypertensive rats. In contrast, Y27632 ((R)-(+)-trans-N-(4-Pyridyl)-4-(1-aminoethyl)cyclohexanecarboxamide) and verapamil, inhibitors of Rho kinase and voltage-dependent Ca2+ channels, respectively, significantly inhibited basal tone but not ERK1/2 activity. Thus, basal vascular tone is elevated by the altered activation of MAPK in DOCA-salt hypertensive rats, and this is regulated by PKC, but not by Rho or intracellular Ca2+.
Kim
Junghwan
J
Department of Physiology, College of Medicine, Institute of Biomedical Science and Technology, Konkuk University, Danwol-dong 322, Choongju 380-701, Korea.
Lee
Youn R
YR
Lee
Chang-Hun
CH
Choi
Won-Ho
WH
Lee
Chang-Kwon
CK
Kim
Jaeheung
J
Bae
Young M
YM
Cho
SungIl
S
Kim
Bokyung
B
D000577:Amides / Q000494:pharmacology; D000818:Animals; D001013:Aorta, Thoracic / Q000502:physiology*; D001794:Blood Pressure / Q000187:drug effects; D003900:Desoxycorticosterone / Q000008:administration & dosage / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005419:Flavonoids / Q000494:pharmacology; D006973:Hypertension / Q000139:chemically induced / Q000503:physiopathology*; D066298:In Vitro Techniques; D007211:Indoles / Q000494:pharmacology; D008297:Male; D008301:Maleimides / Q000494:pharmacology; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology*; D010766:Phosphorylation / Q000187:drug effects; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology; D014700:Verapamil / Q000494:pharmacology
D000577:Amides; D004791:Enzyme Inhibitors; D005419:Flavonoids; D007211:Indoles; D008301:Maleimides; D011725:Pyridines; D014665:Vasodilator Agents; C108830:Y 27632; D012701:Serotonin; D003900:Desoxycorticosterone; D014700:Verapamil; D011493:Protein Kinase C; D020928:Mitogen-Activated Protein Kinases; C070515:bisindolylmaleimide I; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one