LOSS OF ENDOTHELIUM-DEPENDENT RELAXATION IN PROXIMAL PULMONARY-ARTERIES FROM RATS EXPOSED TO CHRONIC HYPOXIA - EFFECTS OF IN-VIVO AND IN-VITRO SUPPLEMENTATION WITH L-ARGININE
C. Carville et al., LOSS OF ENDOTHELIUM-DEPENDENT RELAXATION IN PROXIMAL PULMONARY-ARTERIES FROM RATS EXPOSED TO CHRONIC HYPOXIA - EFFECTS OF IN-VIVO AND IN-VITRO SUPPLEMENTATION WITH L-ARGININE, Journal of cardiovascular pharmacology, 22(6), 1993, pp. 889-896
To explore endothelium-dependent relaxation and the L-arginine (L-ARG)
-nitric oxide (NO) pathway during chronic hypoxia, we examined isolate
d rings from large conduit pulmonary arteries and aorta from rats expo
sed to either room air (N), 3-week hypoxia (H), or 3-week H followed b
y 72-h recovery to normoxia (room air). We examined the vasodilatory a
ctions of acetylcholine (ACh), ionophore A23187, and endothelin-3 (ET-
3) on extrapulmonary left and right branches of pulmonary arteries and
thoracic aorta precontracted by phenylephrine (PE 10(-6) M). Endothel
ium-dependent relaxation of N rat pulmonary arteries and aorta to ACh
and A23187 was abolished in the presence of L-N(G) nitroarginine methy
l ester (L-NAME 10(-4) M) or methylene blue (MB 10(-5) M) but was supp
ressed only partially by N(G)-monomethyl-L-arginine (L-NMMA 5 x 10(-4)
M). In pulmonary arteries but not in aorta, ET-3 induced endothelium-
dependent relaxation that was suppressed by L-NAME, MB, and L-NMMA. Pu
lmonary arteries from H rats did not relax with ET-3. As compared with
those of N rats, they exhibited less relaxation to ACh and A23187, (4
7 +/- 3 vs. 89 +/- 2 and 53 +/- 2 vs. 85 +/- 4%, p < 0.001, respective
ly) but exhibited similar relaxation to the nonendothelium-dependent v
asodilator linsidomine. In contrast, endothelial-relaxation did not di
ffer between N and H rat aorta. In vivo administration of 300 mg/kg L-
ARG to H rats increased plasma levels of L-ARG by 10-fold and arterial
tissue level Of L-ARG by sixfold, and fully restored relaxation to AC
h and ET-3. L-ARG added to the organ bath at a similar concentration h
ad no effect despite a threefold increase in arterial L-ARG. We noted
no difference between arterial tissue level Of L-ARG in rats exposed t
o N, H, or H returned to normoxia (H + N). These data suggest that the
impaired endothelium-dependent relaxation that occurs in large condui
t pulmonary arteries during chronic hypoxia is not related to global L
-ARG depletion depletion despite reversibility of the abnormality afte
r pretreatment with L-ARG.