Roles of endogenous vasodepressor prostaglandins in growth of vascular smooth muscle cells in spontaneously hypertensive rats.
We designed experiments to investigate the roles of endogenous prostaglandins (PG) for the rapid proliferation of vascular smooth muscle cells (VSMC) of spontaneously hypertensive rats (SHR). Both the basal and arachidonate-stimulated vasodepressor PG generations were significantly enhanced in the VSMC of SHR when they were at the 1st or 2nd passage. Conversely, the generating capacity was significantly lowered in the VSMC of SHR when the cells reached the 4th or older generation. Based on the (3H)thymidine uptake and doubling time of VSMC, the decline of PG generating capacity seen in the VSMC of SHR was markedly associated with the increased VSMC growth. Indeed, the stimulation of endogenous vasodepressor PG by arachidonate produced a decrease in (3H)thymidine uptake in the VSMC of Wistar-Kyoto rats, whereas the dose was not sufficient to retard the uptake in SHR. On the other hand, the PG synthesis inhibition by indomethacin, a cyclooxygenase inhibitor, significantly enhanced the uptake by the VSMC of SHR. Thus, these data indicate that the impaired vasodepressor PG system is at least partly responsible for the rapid VSMC growth in SHR.
Ishimitsu
T
T
Department of Medicine, University of Tokyo, Japan.
Uehara
Y
Y
Ishii
M
M
Matsukoa
H
H
Ikeda
T
T
Sugimoto
T
T
D000818:Animals; D001013:Aorta, Thoracic / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D004261:DNA Replication / Q000187:drug effects; D007213:Indomethacin / Q000494:pharmacology; D007700:Kinetics; D009131:Muscle, Smooth, Vascular / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D011453:Prostaglandins / Q000096:biosynthesis / Q000502:physiology*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D013936:Thymidine / Q000378:metabolism; D014316:Tritium
D001095:Arachidonic Acids; D011453:Prostaglandins; D014316:Tritium; D016718:Arachidonic Acid; D013936:Thymidine; D007213:Indomethacin