Dual effects of angiotensin II on cultured vascular smooth muscle cell growth

T. Shimada, Matthew Fabian, H. Nishimura

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Abstract

Fowl show spontaneous elevation of blood pressure and neointima formation of the abdominal aorta at young ages. We reported previously that in domestic fowl (DK DeKalb strain) angiotensin II (ANG II) causes a vasopressor action by releasing catecholamines and a depressor/vasorelaxing action via endothelial receptor by releasing endotheliumderived relaxing factor and cGMP. ANG ll-induced relaxation is minor in young chicks (6-10 wk) and becomes more marked as they mature. We examined whether the effect of ANG II on vascular smooth muscle (VSM) growth also changes with age. The [3H]-thymidine (3H-Thd) incorporation into DNA of cultured VSM cells (first subculture) increased with incubation time (12-30 h). [Asp1,Val5]ANG II (native fowl ANG II, 10-6 M) markedly (226.5 %, P < 0.01) Increased 3H-Thd incorporation into quiescent cultures of VSM cells (kept in serum-free medium) from 6 wk-old chicks. This stimulatory effect was reduced with age (41.4,29.6, and 1.0% at 9,19, and 43 wk of age, respectively). Furthermore, ANG II significantly (45.9%, P < 0.01) attenuated the growth-promoting effect of fetal calf serum in cultured VSM cells from 6-wk-old chicks. This inhibitory effect also decreased in older birds (28.8, 7.5, and 28.0% at 9,19, and 43 wks of age, respectively). ANG II showed neither a growth-stimulatory, nor inhibitory effect In primary cultures of VSM cells from adult birds, nor in cultured neointlmal cells, whereas serum and platelet-derived growth factor (20 ng/ml) increased 3HThd incorporation in both primary and subcultures of VSM cells from adult birds. These results suggest that phenotypic modulation of vascular ANG II receptors or post-receptor properties may have occurred with age/maturation, or in neointmal cells, reflecting the changes of endothelium function (NIH grant HL29364 and AHA grant 92-12400).

Original languageEnglish (US)
JournalFASEB Journal
Volume10
Issue number3
StatePublished - 1996

Fingerprint

angiotensin II
Cell growth
Vascular Smooth Muscle
blood vessels
Angiotensin II
smooth muscle
myocytes
Smooth Muscle Myocytes
Muscle
cell growth
Birds
Growth
Organized Financing
chicks
Thymidine
chickens
thymidine
blood serum
receptors
birds

All Science Journal Classification (ASJC) codes

  • Agricultural and Biological Sciences (miscellaneous)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Biochemistry
  • Cell Biology

Cite this

Dual effects of angiotensin II on cultured vascular smooth muscle cell growth. / Shimada, T.; Fabian, Matthew; Nishimura, H.

In: FASEB Journal, Vol. 10, No. 3, 1996.

Research output: Contribution to journalArticle

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abstract = "Fowl show spontaneous elevation of blood pressure and neointima formation of the abdominal aorta at young ages. We reported previously that in domestic fowl (DK DeKalb strain) angiotensin II (ANG II) causes a vasopressor action by releasing catecholamines and a depressor/vasorelaxing action via endothelial receptor by releasing endotheliumderived relaxing factor and cGMP. ANG ll-induced relaxation is minor in young chicks (6-10 wk) and becomes more marked as they mature. We examined whether the effect of ANG II on vascular smooth muscle (VSM) growth also changes with age. The [3H]-thymidine (3H-Thd) incorporation into DNA of cultured VSM cells (first subculture) increased with incubation time (12-30 h). [Asp1,Val5]ANG II (native fowl ANG II, 10-6 M) markedly (226.5 {\%}, P < 0.01) Increased 3H-Thd incorporation into quiescent cultures of VSM cells (kept in serum-free medium) from 6 wk-old chicks. This stimulatory effect was reduced with age (41.4,29.6, and 1.0{\%} at 9,19, and 43 wk of age, respectively). Furthermore, ANG II significantly (45.9{\%}, P < 0.01) attenuated the growth-promoting effect of fetal calf serum in cultured VSM cells from 6-wk-old chicks. This inhibitory effect also decreased in older birds (28.8, 7.5, and 28.0{\%} at 9,19, and 43 wks of age, respectively). ANG II showed neither a growth-stimulatory, nor inhibitory effect In primary cultures of VSM cells from adult birds, nor in cultured neointlmal cells, whereas serum and platelet-derived growth factor (20 ng/ml) increased 3HThd incorporation in both primary and subcultures of VSM cells from adult birds. These results suggest that phenotypic modulation of vascular ANG II receptors or post-receptor properties may have occurred with age/maturation, or in neointmal cells, reflecting the changes of endothelium function (NIH grant HL29364 and AHA grant 92-12400).",
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