Increased sensitivity of serotonin on the voltage-dependent K+ channels in mesenteric arterial smooth muscle cells of OLETF rats.
This study examined the mechanisms of hypertension in diabetes. We investigated the effects of serotonin (5-HT) on voltage-dependent K(+) (Kv) channel activity, vasoconstriction, 5-HT receptor expression levels, and the involvement of protein kinase C (PKC) in mesenteric arteries of Otsuka Long-Evans Tokushima fatty (OLETF) rats compared with Long-Evans Tokushima Otsuka (LETO) rats. Blood pressure, body weight, blood glucose level, and mesenteric arterial wall thickness were greater in OLETF rats. The 5-HT-induced vasoconstriction of mesenteric arteries was greater in OLETF rats than in LETO rats and inhibited by the 5-HT(2A) inhibitor inhibitor, ketanserin. The Kv currents in mesenteric arterial smooth muscle cells (MASMCs), determined using a perforated patch clamp technique, was inhibited by 1 mM 4-AP (42.5 +/- 4.1% vs. 63.5 +/- 2.3% in LETO vs. OLETF rats at +40 mV), but was insensitive to 1 mM TEA and 100 nM iberiotoxin. The inhibition of Kv current by 1 microM 5-HT in MASMCs was greater in OLETF rats than in LETO rats (17.1 +/- 2.2% vs. 33.2 +/- 2.7% in LETO vs. OLETF rats at +40 mV), and the inhibition was prevented by treatment with the PKCalpha- and beta- selective inhibitor, Gö6976. The expression level of 5-HT(2A), but not 5-HT(2B), receptor and the expression levels of total PKC, PKCbeta, and PKCepsilon, but not PKCalpha, were higher in the mesenteric arteries of OLETF rats compared with LETO rats. The enhanced expression of 5-HT(2A) receptor together with PKCbeta may promote mesenteric vasoconstriction and increase vascular resistance in OLETF rats.
Ko
Eun A
EA
National Research Laboratory for Mitochondrial Signaling, Department of Physiology, College of Medicine, Cardiovascular and Metabolic Disease Center, FIRST Mitochondrial Research Group, Inje University, 633-165 Gaegeum-Dong, Busanjin-Gu, Busan 614-735, Republic of Korea.
Park
Won Sun
WS
Firth
Amy L
AL
Hong
Da Hae
DH
Choi
Seong Woo
SW
Heo
Hye-Jin
HJ
Kim
Min Hee
MH
Noh
Jung Hyun
JH
Ko
Jae-Hong
JH
Kim
Nari
N
Earm
Yung E
YE
Song
Dae Kyu
DK
Han
Jin
J
D000818:Animals; D003920:Diabetes Mellitus / Q000378:metabolism; D004195:Disease Models, Animal; D006973:Hypertension / Q000378:metabolism; D008638:Mesenteric Arteries / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D032389:Myocytes, Smooth Muscle / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D024642:Potassium Channels, Voltage-Gated / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D020334:Rats, Inbred OLETF; D011985:Receptors, Serotonin / Q000378:metabolism; D012701:Serotonin / Q000494:pharmacology*
D024642:Potassium Channels, Voltage-Gated; D011985:Receptors, Serotonin; D012701:Serotonin