[Effects of iptakalim on intracellular calcium concentrations, PKA and PKC activities in rat tail artery smooth muscle cells].
OBJECTIVE
To investigate the effects of iptakalim, a new structural potassium channel opener (KCO), on intracellular calcium concentration ([Ca2+]i), protein kinase C (PKC), and cAMP-dependent kinase (PKA) activities in rat tail artery smooth muscle cells (RTA-SMC), and to analyze mechanisms involved in iptakalim reversing hypertensive vascular remodeling.


METHODS
RTA-SMC was cultured and passages 3-4 were used for experiment. [Ca2+] i was measured by laser scanning confocal microscope after loaded with fluorescent indicator fluo-3-acetoxymethylester, and activities of PKA and PKC were detected by commercial assay kits (the nonradioactive PepTag system) following instructions.


RESULTS
Compared with baseline, [Ca2+] i reduced significantly after iptakalim- or pinacidil-treatment at concentrations of 0.1, 1 and 10 micromol x L(-1), while diazoxide caused significant decrease at concentration of 1 and 10 micromol x L(-1). After preincubation with 1 micromol x L(-1) glibenclamide, [Ca2+] i was not significantly changed when iptakalim, pinacidil or diazoxide were added at concentration of 0.1 and 1 micromol x L(-1). Activities of PKA and PKC increased significantly by 1 micromol x L(-1) iptakalim- or pinacidil-treatment, while 1 micromol x L(-1) diazoxide induced significant change in activity of PKC but not in that of PKA.


CONCLUSIONS
The characteristics of iptakalim on [Ca2+] i, PKA and PKC are more or less similar to those of pinacidil. Iptakalim decreased [Ca2+] i while increased PKA and PKC activities of RTA-SMCs, which may contribute to its ability to reverse antihypertensive vascular remodeling.
Gao
Min
M
Institute of Pharmacology and Toxicology, Academy of Military Medical Sciences, Beijing 100850, China.
Wang
Yu
Y
Wang
Hai
H
D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D003981:Diazoxide / Q000494:pharmacology; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism*; D020110:Pinacidil / Q000494:pharmacology; D011437:Propylamines / Q000494:pharmacology*; D011493:Protein Kinase C / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013623:Tail / Q000098:blood supply
D000959:Antihypertensive Agents; C502260:N-(1-methylethyl)-1,1,2-trimethylpropylamine; D011437:Propylamines; D020110:Pinacidil; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C; D003981:Diazoxide; D002118:Calcium