KATO, S., SATO, S.
and
TAKAHASHI, K.
Almitrine Bismesylate Reduces Hypoxic Pulmonary Vasoconstriction in Isolated Rat Lungs. Tohoku J. Exp. Med., 1989,
157 (2), 119-129-The purpose of this study is to test how almitrine bismesylate (
Alm
) affects the function of pulmonary vasculature during normoxic ventilation,
and
whether low doses of
Alm
not causing detectable vasoconstriction during normoxic ventilation potentiate hypoxic pulmonary vasoconstriction (HPVC). Isolated Wistar male rat lungs were perfused with homologous blood at constant flow,
and
venous
and
ventilatory pressure. In the first experiment, after equilibration, dose-response curves to
Alm
(from 0 to 1000ng/ml,
n=10) were measured under the ventilation with normoxic gas mixture (21% O
2, 5% CO
2, 74% N
2). It was found that
Alm
causes a dose-dependent pulmonary vasoconstriction. In the second experiment, low doses of
Alm
(125ng/ml) or diluent of
Alm
(malic acid) was injected to the blood reservoier. This doses of
Alm
did not cause significant vasoconstriction during normoxic gas ventilation compaired with malic acid. After stabilization of pulmonary arterial pressure, the lungs were exposed to three cycles of normoxia (10min)
and
hypoxia (10min) through ventilation with gas containing 21% or 2% O
2 and
5% CO
2. It was observed that low doses of
Alm
significantly reduce HPVC (
p<0.05) on the later periods of the first
and
the second hypoxic challenges. However, no significant difference was revealed among two groups in the third hypoxic challenge. Directly measured blood
Alm
concentration was significantly lower in the third challenge than in the first challenge. Responses to angiotensin II were not decreased by
Alm
. In conclusion, high doses of
Alm
constrict pulmonary vasculature dose-dependently,
and
low doses of the drug not causing vasoconstriction during normoxia reduce HPVC in rat.
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