Angiotensin II, a
vasoconstrictor, has been previously demonstrated to produce a secondary vasodilatation due to release of
prostaglandins. Because of this effect, we investigated whether infusion of exogenous
angiotensin II via miniosmopumps in rats during a 1-wk exposure to chronic hypobaric
hypoxia might prevent
pulmonary hypertension,
right ventricular hypertrophy, and vascular changes. We instrumented the rats with indwelling cardiovascular
catheters and compared the hemo-dynamic and structural response in animals given
angiotensin II,
indomethacin in addition to
angiotensin II (to block
prostaglandin production), or saline with or without
indomethacin. We then determined whether
angiotensin II infusion also prevents acute hypoxic pulmonary vasoconstriction. We observed that exogenous
angiotensin II infusion abolished the rise in pulmonary artery pressure, the
right ventricular hypertrophy, and the vascular changes induced during chronic
hypoxia in control saline-infused rats with or without
indomethacin. The protective effect of
angiotensin II was lost when
indomethacin was given to block
prostaglandin synthesis. During acute
hypoxia, both
angiotensin II and
prostacyclin infusions similarly prevented the rise in pulmonary artery pressure observed in saline-infused rats and in rats given
indomethacin or
saralasin in addition to
angiotensin II. Thus exogenous
angiotensin II infusion prevents chronic hypoxic
pulmonary hypertension, associated
right ventricular hypertrophy, and vascular changes and blocks acute hypoxic
pulmonary hypertension, and this is likely related to its ability to release
vasodilator prostaglandins.