Am. Roberts et al., Potentiation of pulmonary arteriolar vasoconstriction to endothelin-1 by inhibition of nitric oxide synthesis in the intact lung, MICROCIRCUL, 5(4), 1998, pp. 289-298
Objective: To observe pulmonary arteriolar effects of endothelin-1 (ET-1) i
n the intact lung and determine if constriction to ET-1 is potentiated by i
nbibition of nitric oxide (NO) synthesis.
Methods: In anesthetized male Spragrue-Dawley rats with open chest, the lun
gs were ventilated with air through the lon-er trachea and in vivo response
s of pulmonary arterioles were examined by video microscopy. Observations w
ere made when the lungs were statically inflated with oxygen to a pressure
of approximately 10 cm H2O for brief periods. A lens with a dipping cone wa
s held at the pleural surface. ET-1 (10(-7)-10(-5)M; approximately 0.1 ml)
was applied topically to the fluid layer under the dipping cone.
Results: ET-1 (10(-6)M) constricted parent arterioles 60 +/- 5 mu m in diam
eter by 52 +/- 12% (range: 20-100%) and branches 45 +/- 3 mu m in diameter
by 36 +/- 4% (19-48%). Constriction persisted and there was a dramatic long
-lasting decrease in flow. Alveolar walls quickly became pale, indicating r
educed capillary perfusion. A lower concentration of ET-1 (10(-7)M) constri
cted (p > 0.05) parent arterioles 61 +/- 4 mu m in diameter by 7 +/- 3% ini
tially, and by 13 +/- 8% after 14 +/- 2 minutes, while smaller branches did
not respond. In separate experiments, infusion of the NO synthase inhibito
r L-NAME (1 mg/kg per mim-lte), modestly (10 +/- 3%) decreased (p < 0.05) b
aseline parent arteriolar diameter from 72 +/- 7 mu m to 64 +/- 5 mu m. Bra
nch diameter changed insignificantly from 42 +/- 7 mu m to 38 +/- 7 mu m. A
fter L-NAME, ET-1 (10(-7) M) constricted (p < 0.05) parent arterioles by 17
+/- 4% initially and 40 +/- 14% after 14 +/- 2 minutes. Concurrently, bran
ches constricted (p < 0.05) by 14 +/- 4% and 26 +/- 15%.
Conclusions: Arterioles less than 80 mu m in diameter were very responsive
to ET-1. which could be a factor in altering pulmonary microvascular resist
ance. Inhibition of NO synthesis appears to potentiate constriction to ET-1
.