Rapid smooth muscle cell growth and endogenous prostaglandin system in spontaneously hypertensive rats.
Vascular smooth muscle cells (VSMC) from spontaneously hypertensive rats (SHR) exhibit rapid cell growth. In this study, to reveal the mechanisms of the quick VSMC growth, we analyzed the alterations in the respective periods of the proliferating cell cycle, and investigated the role of the endogenous prostaglandin system in this rapid cell growth. The VSMC from SHR showed increased [3H]thymidine uptake and shortened doubling time, compared with Wistar-Kyoto rats (WKY). These properties were mainly due to both shortened transition time from G0/G1 to S and shortened G2 duration. There was a difference neither in the DNA-replication rate nor in the mitotic period. Generating capacity for vasodepressor prostaglandins was significantly reduced in the VSMC from SHR, particularly in the G0/G1 period. When the endogenous prostaglandin synthesis was inhibited by 10(-5) mol/L indomethacin, the transition from G0/G1 to S was shortened. This alteration was eliminated by supplementation with OP41483, a stable prostacyclin analog. In contrast, the alteration in the G2 duration was unaffected by indomethacin. These data indicate that the rapid VSMC growth in SHR is mainly due to the shortening of both the G0/G1 and G2 period, and that the impaired prostaglandin system is responsible, at least in part, for the shortened G0/G1 duration.
Uehara
Y
Y
Second Department of Medicine, University of Tokyo, Japan.
Numabe
A
A
Kawabata
Y
Y
Nagata
T
T
Hirawa
N
N
Ishimitsu
T
T
Matsuoka
H
H
Ikeda
T
T
Sugimoto
T
T
D000818:Animals; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D003505:Cyclodextrins / Q000494:pharmacology; D004247:DNA / Q000378:metabolism; D011464:Epoprostenol / Q000031:analogs & derivatives / Q000494:pharmacology; D016193:G1 Phase / Q000187:drug effects / Q000502:physiology; D006973:Hypertension / Q000473:pathology / Q000503:physiopathology*; D007213:Indomethacin / Q000494:pharmacology; D008940:Mitotic Index; D009131:Muscle, Smooth, Vascular / Q000166:cytology* / Q000502:physiology; D011453:Prostaglandins / Q000502:physiology*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D016192:Resting Phase, Cell Cycle / Q000187:drug effects / Q000502:physiology; D016196:S Phase / Q000187:drug effects / Q000502:physiology; D013936:Thymidine / Q000378:metabolism; D014316:Tritium; D047391:alpha-Cyclodextrins
D003505:Cyclodextrins; D011453:Prostaglandins; D047391:alpha-Cyclodextrins; D014316:Tritium; C051518:OP 41483-alpha-cyclodextrin; D004247:DNA; D011464:Epoprostenol; D013936:Thymidine; D007213:Indomethacin