[Role of external calcium on the growth of aortic smooth muscle cells in SHR].
Cultured aortic smooth muscle cells from SHR proliferate more actively than cells normotensive control animals. This experimental data may be related to the hypertensive arteriopathy which mainly proceeds from media dystrophy made of hypertrophy, hyperplasia and excessive protein secretion of the smooth muscle cells. In order to precise the molecular cause of the phenomenon and the eventual action of calcium channel blockers on the development of this organic characteristic of hypertension, we have compared the responses of cultured cells from both SH and WKY rats to various agents in the absence or presence of verapamil. Cell proliferation, phospholipase C activation, and c-jun and c-fos oncogene expressions were measured in both cultures under the same conditions. The mitogenic actions of both foetal calf serum (FCS) and angiotensin II are two times more important on SH than on WKY rat cells. However, while inositol phosphate production elicited by angiotensin in also doubled in SHR cultures versus WKY ones. FCS-induced PLC activation is equivalent in both types of cells. The proto-oncogenes are more intensively expressed when WKY cells are stimulated by FCS than in the presence of angiotensin, but, contrarily to angiotensin, serum is not more active upon this parameter in SHR cultures. Verapamil (from 10(-8) M to 10(-5) M) decreases by 30% the proliferative effect of serum in both SH and WKY rat cells but is not significantly active on angiotensin stimulation. It also depresses in the same proportion the serum-induced inositol phosphate production and oncogene expressions without altering the responses to angiotensin. Nicardipine is less active than verapamil.(ABSTRACT TRUNCATED AT 250 WORDS)
Paquet
J L
JL
INSERM U 7, hôpital Necker, Paris.
Brunelle
G
G
Donnadieu
E
E
Baudouin-Legros
M
M
Meyer
P
P
D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D001011:Aorta; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D006973:Hypertension / Q000473:pathology*; D008938:Mitosis / Q000187:drug effects; D024510:Muscle Development; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000254:growth & development*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D014700:Verapamil / Q000494:pharmacology
D000804:Angiotensin II; D014700:Verapamil; D002118:Calcium
Rôle du calcium externe sur la croissance des cellules musculaires lisses aortiques de SHR.