M and B 22948, a cGMP phosphodiesterase inhibitor, is a pulmonary vasodilator in lambs

Dana Braner, J. R. Fineman, R. Chang, S. J. Soifer

Research output: Contribution to journalArticle

89 Citations (Scopus)

Abstract

To investigate the hypothesis that pulmonary vascular tone and endothelium-dependent pulmonary vasodilation are mediated by changes in the vascular smooth muscle cell concentration of cGMP, we studied the hemodynamic effects of M and B 22948, a selective guanosine 3',5'-cyclic monophosphate (cGMP) phosphodiesterase inhibitor, in eight intact newborn lambs. At rest, M and B 22948 (1.0-2.5 mg/kg) selectively decreased pulmonary arterial pressure (by 8.5 ± 6.6 to 10.3 ± 4.5%, P <0.05). Similarly, M and B 22948 (0.5-5.0 mg/kg) produced selective dose-dependent decreases in pulmonary arterial pressure during pulmonary hypertension induced either by U46619 (by 7.7 ± 4.2 to 44.2 ± 4.4%, P <0.05) or by alveolar hypoxia (by 9.5 ± 6.2 to 29.0 ± 11.0%, P <0.05). In addition, M and B 22948 augmented the pulmonary vasodilating effects of acetylcholine and ATP (both endothelium- and cGMP- dependent vasodilators) but not isoproterenol (an endothelium-independent and cAMP-dependent vasodilator). Because M and B 22948 inhibits the breakdown of cGMP, this study supports the in vitro data that changes in the vascular smooth muscle cell concentration of cGMP, in part, may regulate pulmonary vascular tone and mediate endothelium-dependent vasodilator responses in the pulmonary circulation. In addition, N(ω)-nitro-L-arginine (an inhibitor of endothelium-derived relaxing factor synthesis) blocked the vasodilating effects of M and B 22948, suggesting that the majority of endogenous cGMP is generated by the release of endothelium-derived relaxing factor.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume264
Issue number1 33-1
StatePublished - 1993
Externally publishedYes

Fingerprint

Phosphodiesterase Inhibitors
Vasodilator Agents
Endothelium-Dependent Relaxing Factors
Lung
Vascular Smooth Muscle
Smooth Muscle Myocytes
Arterial Pressure
15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid
Pulmonary Circulation
Cyclic GMP
Vascular Endothelium
Isoproterenol
Pulmonary Hypertension
Vasodilation
Acetylcholine
Endothelium
Blood Vessels
Arginine
zaprinast
Adenosine Triphosphate

Keywords

  • endothelium-derived relaxing factor
  • N(ω)-nitro-L-arginine
  • pulmonary hypertension

ASJC Scopus subject areas

  • Physiology

Cite this

M and B 22948, a cGMP phosphodiesterase inhibitor, is a pulmonary vasodilator in lambs. / Braner, Dana; Fineman, J. R.; Chang, R.; Soifer, S. J.

In: American Journal of Physiology - Heart and Circulatory Physiology, Vol. 264, No. 1 33-1, 1993.

Research output: Contribution to journalArticle

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abstract = "To investigate the hypothesis that pulmonary vascular tone and endothelium-dependent pulmonary vasodilation are mediated by changes in the vascular smooth muscle cell concentration of cGMP, we studied the hemodynamic effects of M and B 22948, a selective guanosine 3',5'-cyclic monophosphate (cGMP) phosphodiesterase inhibitor, in eight intact newborn lambs. At rest, M and B 22948 (1.0-2.5 mg/kg) selectively decreased pulmonary arterial pressure (by 8.5 ± 6.6 to 10.3 ± 4.5{\%}, P <0.05). Similarly, M and B 22948 (0.5-5.0 mg/kg) produced selective dose-dependent decreases in pulmonary arterial pressure during pulmonary hypertension induced either by U46619 (by 7.7 ± 4.2 to 44.2 ± 4.4{\%}, P <0.05) or by alveolar hypoxia (by 9.5 ± 6.2 to 29.0 ± 11.0{\%}, P <0.05). In addition, M and B 22948 augmented the pulmonary vasodilating effects of acetylcholine and ATP (both endothelium- and cGMP- dependent vasodilators) but not isoproterenol (an endothelium-independent and cAMP-dependent vasodilator). Because M and B 22948 inhibits the breakdown of cGMP, this study supports the in vitro data that changes in the vascular smooth muscle cell concentration of cGMP, in part, may regulate pulmonary vascular tone and mediate endothelium-dependent vasodilator responses in the pulmonary circulation. In addition, N(ω)-nitro-L-arginine (an inhibitor of endothelium-derived relaxing factor synthesis) blocked the vasodilating effects of M and B 22948, suggesting that the majority of endogenous cGMP is generated by the release of endothelium-derived relaxing factor.",
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