Mg. Persson et al., OXYGEN OR LOW CONCENTRATIONS OF NITRIC-OXIDE REVERSE PULMONARY VASOCONSTRICTION INDUCED BY NITRIC-OXIDE SYNTHESIS INHIBITION IN RABBITS, Acta Physiologica Scandinavica, 150(4), 1994, pp. 405-411
The objective of this study was to investigate the role of nitric oxid
e and oxygen in the regulation of pulmonary vascular resistance, espec
ially by means of substitution with nitric oxide after inhibition of e
ndogenous nitric oxide formation. In artificially ventilated open-ches
t rabbits pulmonary vascular resistance at normoxic ventilation (FIO2
= 21%) was 56 +/- 6 cmH(2)O ml(-1) min(-1) 1000(-1) (mRU(L)). N-omega-
nitro-L-arginine methyl ester (L-NAME, 30 mg kg(-1)), an inhibitor of
NO synthase, increased pulmonary vascular resistance to 122 +/- 17 mRU
(L) at normoxic ventilation. In response to L-NAME there was also an i
ncrease in mean arterial blood pressure. Exogenous nitric oxide (0.014
-9 p.p.m. in the inhaled air) dose-dependently and reversibly countera
cted the effect of L-NAME on pulmonary vascular resistance at normoxic
ventilation, without affecting systemic brood pressure. In addition,
the L-NAME-induced vasoconstriction was critically dependent on oxygen
. Thus, during hypoxic ventilation (FIO2 = 10%) the pulmonary vascular
resistance was increased approximately four-fold by the presence of L
-NAME (30mg kg(-1)), and increments in FIO2 (21-100%) dose-dependently
and reversibly counteracted the effect of L-NAME on pulmonary vascula
r resistance. Taken together these findings demonstrate that inhalatio
n of low doses of NO may act as a replacement when endogenous NO synth
esis is inhibited, and that pulmonary vasoconstriction induced by NO s
ynthesis inhibition is likely to be the result of interference with ox
ygen-dependent regulatory mechanisms. Endogenous NO cooperates with ox
ygen to evoke a vasodilator component of the pulmonary hypoxic presser
response, balancing a hitherto unknown constrictor mechanism.