Quinapril inhibits c-Myc expression and normalizes smooth muscle cell proliferation in spontaneously hypertensive rats.
A number of data suggest that angiotensin II-dependent activation of the protooncogene c-myc participates in the proliferative response of smooth muscle cells (SMC) of rats with spontaneous hypertension (SHR). We therefore investigated the effects of chronic treatment with the angiotensin converting enzyme (ACE) inhibitor quinapril on the oncoprotein c-Myc and the proliferating cell nuclear antigen cyclin A in SMC of small intramyocardial arteries from the left ventricle of SHR. The expression of c-Myc and cyclin A was assessed by immunocytochemical analysis. The number of smooth muscle cells was assessed by morphometrical analysis. As compared to normotensive Wistar-Kyoto (WKY) rats, untreated SHR exhibited an increased percentages of cells expressing c-Myc (33% +/- 4% v 19% +/- 2%, mean +/- SEM, P < .005) and cyclin A (25 +/- 2 v 11% +/- 1%, P < .001). In quinapril-treated SHR compared with untreated SHR, we found decreased expression of c-Myc (22% +/- 2%, P < .005) and cyclin A (13% +/- 1%, P < .001). No significant differences were found between WKY rats and quinapril-treated SHR in the above parameters. Cyclin A was directly correlated with the number of SMCs in each group of rats. These results suggest that an enhanced expression of c-Myc may be involved in the increased proliferation seen in SMCs from small arteries of SHR. Quinapril administration normalizes proliferation in the SMCs of SHR, possibly by inhibiting the expression of the oncoprotein c-Myc and its effects on the cell cycle.
Díez
J
J
Vascular Pathophysiology Unit, School of Medicine, University of Navarra, Spain.
Panizo
A
A
Hernández
M
M
Galindo
M F
MF
Cenarruzabeitia
E
E
Pardo Mindán
F J
FJ
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D019925:Cyclin A / Q000032:analysis; D006973:Hypertension / Q000378:metabolism / Q000473:pathology*; D007546:Isoquinolines / Q000494:pharmacology*; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000473:pathology; D016271:Proto-Oncogene Proteins c-myc / Q000032:analysis*; D000077583:Quinapril; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D044005:Tetrahydroisoquinolines
D000806:Angiotensin-Converting Enzyme Inhibitors; D019925:Cyclin A; D007546:Isoquinolines; D016271:Proto-Oncogene Proteins c-myc; D044005:Tetrahydroisoquinolines; D000077583:Quinapril