Inhaled nitric oxide: dose response and the effects of blood in the isolated rat lung.
Inhaled nitric oxide (NO) is a vasodilator selective to the pulmonary circulation. Using isolated rat lungs, we determined the dose-response relationship of NO and the role of blood in mediating pulmonary vasodilation and selectivity. Inhaled 20, 50, 100, and 1,000 ppm NO attenuated (P < 0.001) hypoxic pulmonary vasoconstriction by 16.1 +/- 4.9, 22.6 +/- 6.8, 28.4 +/- 3.5, and 69.3 +/- 4.2%, respectively. Inhaled 13, 34, 67, and 670 ppm NO attenuated the increase in pulmonary arterial pressure secondary to angiotensin II more (P < 0.001) in Greenberg-Bohr buffer- (GB) than in blood-perfused lungs (51.7 +/- 9.9, 71.9 +/- 8.9, 78.2 +/- 5.3, and 91.9 +/- 2.1% vs. 14.3 +/- 4.1, 23.8 +/- 4.6, 28.4 +/- 3.8, and 55.5 +/- 5.9%, respectively). Samples from GB- but not blood-perfused lungs contained NO (93.0 +/- 26.3 nM). Intravascular NO attenuated the response to angiotensin II more (P < 0.001) in GB- (with and without plasma) than in blood- (hematocrit = 41 and 5%) perfused lungs (75.6 +/- 6.4 and 70.9 +/- 4.8% vs. 22.2 +/- 2.4 and 39.4 +/- 7.6%). In conclusion, inhaled NO produces reversible dose-dependent pulmonary vasodilation over a large range of concentrations. Inhaled NO enters the circulation, but red blood cells prevent systemic vasodilation and also a significant amount of pulmonary vasodilation.
Rich
G F
GF
Department of Anesthesiology, University of Virginia Health Sciences Center, Charlottesville 22908.
Roos
C M
CM
Anderson
S M
SM
Urich
D C
DC
Daugherty
M O
MO
Johns
R A
RA
D000280:Administration, Inhalation; D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D001790:Blood Physiological Phenomena; D004305:Dose-Response Relationship, Drug; D000860:Hypoxia / Q000503:physiopathology; D066298:In Vitro Techniques; D008297:Male; D009569:Nitric Oxide / Q000097:blood / Q000494:pharmacology*; D011652:Pulmonary Circulation / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014664:Vasodilation / Q000502:physiology
D000804:Angiotensin II; D009569:Nitric Oxide