Pulmonary vascular reactivity in hyperoxic pulmonary hypertension in the rat.
Breathing 87% O2 for 7 days causes pulmonary vascular remodeling and pulmonary hypertension in the rat. In the isolated perfused lung of the normal and O2-exposed rat, change in pre- and postcapillary resistance was determined in response to challenge with angiotensin II (ANG II; 5, 25, and 50 micrograms) or histamine (0.5 and 1.0 microgram). In the hyperoxic lung both pre- and postcapillary resistance were increased at base line, although the latter less consistently so. In response to each agent precapillary resistance increased more than postcapillary resistance in the hyperoxic lung. In the normal lung pre- and postcapillary reactivity to histamine were similar but the latter was the greater in response to ANG II. In the hyperoxic lung only the pre- and postcapillary response to the first challenge of ANG II (5 micrograms) was greater than normal. The magnitude of the precapillary response was not related to the level of base-line resistance, and this response was significantly increased in a small number of hyperoxic lungs with base-line resistance in the normal range. Tachyphylaxis occurred after the first dose of ANG II. In the hyperoxic lung only the precapillary response to 0.5 micrograms histamine was greater than normal. We conclude that exposure to hyperoxia for 7 days causes an increase in pulmonary arterial reactivity. Furthermore, the alteration in reactivity is not caused by vascular restriction. We hypothesize that it is attributable to peripheral extension of smooth muscle in alveolar wall arteries.
Gore
R G
RG
Department of Pathology, Children's Hospital, Boston, Massachusetts.
Jones
R
R
D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D006632:Histamine / Q000494:pharmacology; D006976:Hypertension, Pulmonary / Q000503:physiopathology*; D066298:In Vitro Techniques; D008297:Male; D010100:Oxygen; D010477:Perfusion; D011652:Pulmonary Circulation / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D014655:Vascular Resistance / Q000187:drug effects; D014661:Vasoconstriction / Q000187:drug effects
D000804:Angiotensin II; D006632:Histamine; D010100:Oxygen