CONTROL OF VASCULAR SMOOTH-MUSCLE CELL-GROWTH IN FOWL

In adult domestic fowl, angiotensin (ANG) receptors are present in the vascular smooth muscles (VSM) and in the endothelium, mediating vasor elaxation via endothelium-derived relaxing factor/cGMP ANG II-induced relaxation is minor in chicks and becomes more marked as they mature b ut diminishes in adult birds, whereas ANG II neither relaxes nor contr acts endothelium-denuded aortae from mature chickens. The present stud y examines in cultured fowl aortic SM cells whether (1) ANG II stimula tes or inhibits VSM cell growth and, if so, whether this growth-stimul atory or -inhibitory effect changes with maturation/aging, and (2) S-n itroso-N-acetylpenicillamine (SNAP), a nitric oxide donor, and cGMP at tenuate the basal or stimulated VSM cell growth. [Asp(1), Val(5)]ANG I I (native fowl ANG II, 10(-6) hi) markedly increased (increase from ve hicle control, 226.5%; P < 0.01) [H-3]thymidine (Thd) incorporation in to DNA of quiescent VSM cells (first subculture) from 6-week-old chick s. This growth-stimulating effect was reduced with age (41.4, 29.6, an d 3.2% at 9, 19, and 43 weeks of age, respectively). In contrast, plat elet-derived growth factor (PDGF, 20 ng/ml) increased [H-3]Thd incorpo ration similarly in chicks, pullers, and hens. Furthermore, ANG II sig nificantly (45.9%, P < 0.01) attenuated the growth-promoting effect of fetal calf serum in cultured VSM cells from 6-week-old chicks. This i nhibitory effect also decreased in older birds. ANG II showed neither a growth-stimulatory nor -inhibitory effect in cultured neointimal cel ls. SNAP attenuated dose dependently (20-60 mu M) the basal and PDGF-i nduced VSM cell growth, whereas cGMP inhibited basal growth only at a high dose (100 mu M). These results indicate that in fowl VSM cells, A NG II is mitogenic and antimitogenic in chicks but not in mature birds , suggesting that phenotypic modulation occurs in the ANG receptors/si gnaling mechanism with maturation/age or in neointimal cells, whereas the mitogenic mechanism via PDGF remains in both young and mature bird s. (C) 1998 Academic Press.