Angiotensin II prevents hypoxic pulmonary hypertension and vascular changes in rat.
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.
Rabinovitch
M
M
Research Institute, Hospital for Sick Children, Toronto, Ontario, Canada.
Mullen
M
M
Rosenberg
H C
HC
Maruyama
K
K
O'Brodovich
H
H
Olley
P M
PM
D000208:Acute Disease; D000804:Angiotensin II / Q000627:therapeutic use*; D000818:Animals; D001808:Blood Vessels / Q000473:pathology; D002908:Chronic Disease; D006976:Hypertension, Pulmonary / Q000517:prevention & control*; D000860:Hypoxia / Q000150:complications*; D007262:Infusions, Intravenous; D008297:Male; D011652:Pulmonary Circulation / Q000187:drug effects*; D051381:Rats; D011919:Rats, Inbred Strains
D000804:Angiotensin II