Mr. Maclean et al., EFFECTS OF PULMONARY-HYPERTENSION ON VASOCONSTRICTOR RESPONSES TO ENDOTHELIN-1 AND SARAFOTOXIN S6C AND ON INHERENT TONE IN RAT PULMONARY-ARTERIES, Journal of cardiovascular pharmacology, 26(5), 1995, pp. 822-830
Vasoconstrictor responses to endothelin-l (ET-1) and the ET(B) recepto
r agonist sarafotoxin S6c (SXS6c) were investigated in the main pulmon
ary artery and pulmonary artery branch removed from rats previously ex
posed to 10% O-2, [chronic hypoxic (CH) rats] or room air (control rat
s) for 2 weeks, The effects of nitric oxide synthase (NOS) inhibition
with L-N-omega-nitroarginine methyl ester (L-NAME) (100 mu M) On ET re
ceptor-induced responses in these arteries were also investigated. In
control rats, in rings of main pulmonary arteries and pulmonary artery
branches, ET-1 induced vasoconstrictor responses. These responses wer
e mediated by the ET(A) receptor as they were antagonized by the ET(A)
receptor antagonist FR 139317 whereas SXS6c did not vasoconstrict. Ch
ronic hypoxia had no effect on the sensitivity of the main pulmonary a
rteries to ET-1, whereas small vasoconstrictor responses to SXS6c were
evident. ET-1 was more potent in the CH rat pulmonary artery branches
than in controls. SXS6c also caused vasoconstriction with a maximum r
esponse 30% of that to ET-I in both endothelium-intact and endothelium
-denuded vessels, L-NAME increased the sensitivity to ET-1 in the CH r
at main pulmonary arteries and increased the responses to low concentr
ations of ET-1 in the control rat main pulmonary arteries but did not
affect any ET-1 responses in any other vessels. It did disclose respon
ses to SXS6c in control rat main pulmonary arteries, L-NAME itself inc
reased vascular tone to a greater extent in CH rat pulmonary arteries
than in controls. In preconstricted pulmonary arteries, however, relax
ations to acetylcholine (ACh) were diminished in the CH rats as compar
ed with their controls. All pulmonary artery branches, denuded of thei
r vascular endothelium, relaxed to sodium nitroprusside (SNP) and ther
efore exhibited endogenous vascular tone. This effect was greatest in
the pulmonary artery branches from the CH rats, The results suggest th
at rat large pulmonary artery responses to ET-1 are normally mediated
by ET(A) receptors. Pulmonary hypertension can potentiate ET(A) recept
or-mediated vasoconstriction and facilitate ET(B) receptor-mediated va
soconstriction. Endogenous NO may normally suppress ET(A) receptor-med
iated responses in rat main pulmonary arteries, Rat pulmonary arteries
exhibit endogenous tone, which is increased by exposure to chronic hy
poxia.