Nipradilol inhibits rat mesangial cell mitogenesis through the activation of soluble guanylate cyclase.
Nipradilol is a beta-adrenoreceptor blocking agent, whose structure contains an NO2 group. Thus, it is possible that it modulates the function of glomerular mesangial cells through the activation of soluble guanylate cyclase. To prove this hypothesis, we examined the effect of nipradilol on soluble guanylate cyclase, intracellular cyclic guanosine monophosphate (cGMP) accumulation, and the mitogenesis of cultured rat glomerular mesangial cells. Nipradilol increased intracellular cGMP accumulation in a dose-dependent manner through the activation of soluble guanylate cyclase. Furthermore, nipradilol inhibited the incorporation of [3H]thymidine into the mesangial cells stimulated by 2.5% fetal bovine serum in a dose-dependent manner. These results indicate that nipradilol may modulate mesangial cell function through an increase in intracellular cGMP resulting from the activation of soluble guanylate cyclase.
Koya
D
D
Third Department of Medicine, Shiga University of Medical Science, Japan.
Kikkawa
R
R
Haneda
M
M
Uzu
T
T
Sawada
M
M
Kajiwara
N
N
Sakamoto
K
K
Sugimoto
T
T
Shigeta
Y
Y
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D002455:Cell Division / Q000187:drug effects*; D002478:Cells, Cultured; D006152:Cyclic GMP / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D005920:Glomerular Mesangium / Q000166:cytology / Q000187:drug effects*; D006162:Guanylate Cyclase / Q000378:metabolism*; D008297:Male; D011412:Propanolamines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D000319:Adrenergic beta-Antagonists; D011412:Propanolamines; D006162:Guanylate Cyclase; C036089:nipradilol; D006152:Cyclic GMP