[Effects of praeruptorin C on cell hypertrophy, intracellular [Ca2+]i, nitric oxide and signal transduction in isolated hypertrophied rat smooth muscle cells induced by angiotensin II].
OBJECTIVE
To investigate the effects of praeruptorin C (Pra-C) on smooth muscle cell (SMC) hypertrophy, intracellular calcium ([Ca2+]i), nitric oxide (NO) content and influence on cellular signal transduction in isolated cultured rat smooth muscle cell (SMC).


METHODS
Hypertrophied smooth muscle cells (HSMCs) were induced by angiotensin II (Ang II), cell area was measured under inverted microscope. Nitric oxide (NO) concentration was measured using Griess method. [Ca2+]i was measured using Fura-2/AM. The responses to [Ca2+]i elevation stimulated by KCl (60 mmol.L-1 or norepinephrine (10 mumol.L-1) were observed by incubation with phorbol 12-myristate 13-acetate (PMA), staurosporine (ST), the agonist and inhibitor of protein kinase C (PKC), and pertussis toxin (PTX), the sensitive toxin of Gi.


RESULTS
The cell area of SMCs were decreased by 39.01% (P < 0.001) and NO content of SMCs were significantly increased in Pra-C + Ang II group. In presence of 60 mmol.L-1 KCl or 10 mumol.L-1 NE, [Ca2+]i of SMCs in Pra-C + Ang II group was significantly decreased than that of Ang II group (P < 0.001) and closed to the normal group. Incubation of SMCs with PMA, ST and PTX, [Ca2+]i of SMCs in Ang II group was increased by PMA and decreased by ST and PTX, but that of Pra-C + Ang II group was similar to the normal group.


CONCLUSIONS
These findings suggest that Pra-C can reduce vascular hypertrophy in isolated rat HSMCs, and this is associated with improvement of SMCs [Ca2+]i level, NO content and cellular signal transdution of PKC and Gi.
Rao
Man-ren
MR
Department of Cardiovascular Pharmacology, Nanjing Medical University, Nanjing 210029, China.
Liu
Wan-bin
WB
Zhang
Xiao-wen
XW
D000804:Angiotensin II; D000818:Animals; D001011:Aorta / Q000473:pathology; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002478:Cells, Cultured; D003374:Coumarins / Q000494:pharmacology*; D005260:Female; D006984:Hypertrophy / Q000139:chemically induced / Q000473:pathology; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D032389:Myocytes, Smooth Muscle / Q000187:drug effects* / Q000473:pathology; D009569:Nitric Oxide / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects*
D002121:Calcium Channel Blockers; D003374:Coumarins; D000804:Angiotensin II; D009569:Nitric Oxide; C058808:praeruptorin C; D002118:Calcium