Decreased insulin-sensitive Ca2+ transport in cultured vascular smooth muscle cells from spontaneously hypertensive rats.
To investigate the role of insulin on Ca2+ regulation of vascular smooth muscle cells (VSMC) in hypertension, the effect of insulin on Ca2+ transport and intracellular free calcium concentration ([Ca2+]i) was measured in cultured VSMC from spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY). Insulin produced a substantial increase in 45Ca uptake as well as [Ca2+]i in quiescent cultured VSMC. The stimulatory effects of insulin were completely inhibited by diltiazem, and partially by H-7, TMB-8, and 5-N,N(hexamethylene)amiloride (HMA), but not by W-7 or trifluoroperazine. Insulin-sensitive 45Ca uptake of SHR VSMC was significantly smaller than that of WKY VSMC. Insulin-sensitive increase in [Ca2+]i of SHR VSMC was also smaller than that of WKY VSMC. It is concluded that insulin increases 45Ca uptake, leading to an increase in [Ca2+]i, presumably through the voltage-dependent Ca2+ channel, intracellular Ca2+ release, or protein kinase C mediated mechanisms in cultured VSMC. A blunted response of insulin-sensitive Ca2+ uptake and [Ca2+]i in SHR VSMC suggests the differential regulation of Ca2+ transport in response to insulin in primary hypertension.
Kuriyama
S
S
Second Department of Internal Medicine, Jikei University School of Medicine, Tokyo, Japan.
Nakamura
K
K
Horiguchi
M
M
Uchida
H
H
Sakai
O
O
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D000584:Amiloride / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D001692:Biological Transport / Q000187:drug effects / Q000502:physiology; D002118:Calcium / Q000493:pharmacokinetics*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002132:Calcium Radioisotopes; D002478:Cells, Cultured; D004110:Diltiazem / Q000494:pharmacology; D005707:Gallic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D006706:Homeostasis; D006973:Hypertension / Q000378:metabolism* / Q000503:physiopathology; D007328:Insulin / Q000494:pharmacology*; D007546:Isoquinolines / Q000494:pharmacology; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000166:cytology* / Q000378:metabolism / Q000502:physiology; D010879:Piperazines / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000502:physiology; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY
D002121:Calcium Channel Blockers; D002132:Calcium Radioisotopes; D007328:Insulin; D007546:Isoquinolines; D010879:Piperazines; C057360:5-(N,N-hexamethylene)amiloride; C006014:8-(N,N-diethylamino)octyl-3,4,5-trimethoxybenzoate; D005707:Gallic Acid; D000584:Amiloride; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D011493:Protein Kinase C; D004110:Diltiazem; D002118:Calcium