[Changes of angiotensin II autocrine by cultured pulmonary artery smooth muscle cells exposed to anoxia].
Alterations of autocrine function of pulmonary arterial smooth muscle cells (PASMCs) might play an important role in development of hypoxic pulmonary hypertension (HPH). To test this hypothesis, the effects of hypoxia on angiotensin II (AT II) secretion by cultured new born bovine PASMCs were investigated. AT II secretion decreased significantly when PASMCs were incubated under 2.5% O2 hypoxic condition for 3 to 48 h (P < 0.01 vs control), but decreased further under anoxic condition (P < 0.01 vs control and 2.5% O2 group). Nitric oxide (NO) donor SIN-1 inhibited AT II secretion significantly under normoxic condition, but NO synthase inhibitor L-nitro-arginine (LNA) eliminated the inhibitory effect of anoxia on AT II autocrine and promoted AT II release. It was also found that the concentration of cGMP in PASMCs increased significantly (P < 0.01) at 24 h incubation in 0% O2, an effect that can be attenuated by LNA. Hypoxia stimulated 3H-TdR incorporation of PASMCs significantly (P < 0.001), while captopril exerts an inhibition in normoxic condition (P < 0.001), but without effect under hypoxic condition. The above results suggest that hypoxia can inhibit AT II secretion by inducing endogenous NO production in PASMCs. AT II autocrine is not involved in hypoxic proliferation of PASMCs, but a decrease of AT II may contribute to prevention of the development of HPH.
Wang
P Y
PY
Research Laboratory of High Altitude Medicine, Department of Pathophysiology, Third Military Medical College, Chongqing 400038.
Liu
J
J
Yu
Z H
ZH
Xu
S M
SM
Luo
D C
DC
Sun
B Y
BY
D000804:Angiotensin II / Q000378:metabolism*; D000818:Animals; D000831:Animals, Newborn; D002417:Cattle; D015687:Cell Hypoxia; D002478:Cells, Cultured; D009131:Muscle, Smooth, Vascular / Q000166:cytology*; D009569:Nitric Oxide / Q000378:metabolism*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D011651:Pulmonary Artery / Q000166:cytology
D020030:Nitric Oxide Donors; D000804:Angiotensin II; D009569:Nitric Oxide