Involvement of Cyclic AMP in Vasodilatation by Amrinone: A Comparative Study with 3-Isobutyl-1-Methyl-Xanthine (IBMX)

Kishi, Yukio; Numano, Fujío

doi:10.1254/jjp.42.477

Cited by 3 publications

(1 citation statement)

References 24 publications

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“…of cyclic AMP PDE, but not of cyclic GMP PDE (Schoeffter et al, 1987). Many other functional studies have shown good correlation between the effectiveness of selective PDE isoenzyme inhibitors on cyclic AMP PDE activity and their effect on contractile activity in cardiac muscle or relaxation of smooth muscle (Polson et al, 1982;Weishaar et al, 1985b;Kishi and Numano, 1986;Kauffman et al, 1987;Miller and Wells, 1987;Marsh et al, 1988;Fujimoto and Matsuda, 1990;Torphy and Cieslinski, 1990;Cheng and Dage, 1991).…”

Section: Introductionmentioning

confidence: 99%

Role of phosphodiesterase isoenzymes in regulating intracellular cyclic AMP in adenosine-stimulated smooth muscle cells

Xiong

Westhead

Slakey

1995

Biochemical Journal

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Three phosphodiesterase (PDE) isoenzymes were separated by Mono Q h.p.l.c. column chromatography from the soluble fraction of a homogenate of pig aortic smooth muscle cells. The first peak of PDE activity was stimulated by calmodulin in the presence of calcium. The second broad peak contained at least two activities, which were sensitive to inhibition by CI-930 or rolipram respectively. The distribution of total cellular enzyme activity in different subcellular fractions was also determined. The majority (78%) of the total activity was present in the cytosolic fraction, 18% of activity was in a membrane-bound form and 4% of activity was associated with the cytoskeleton. Rolipram-sensitive PDE was present predominantly in the cytosolic fraction, whereas cyclic GMP-inhibited, CI-930-sensitive PDE was evenly distributed between the cytosolic and particulate fractions. All of the calmodulin-dependent PDE activity was found in the soluble fraction. CI-930 and rolipram enhanced, by 2-fold and 3-4-fold respectively, the adenosine-stimulated rise in cellular cyclic AMP level. The increase in cyclic AMP levels due to CI-930 or rolipram was dose-dependent. Removal of adenosine once cyclic AMP had risen resulted in a rapid fall in cyclic AMP levels even in the presence of rolipram and CI-930. M&B 22,948, the calmodulin-dependent PDE inhibitor, caused less than a 25% increase of the adenosine-stimulated cyclic AMP levels by itself, but it contributed substantially to controlling the cyclic AMP levels after the removal of adenosine when used together with CI-930 and rolipram. These phenomena suggested that all three PDE isoenzymes participated in modulating cellular cyclic AMP levels after adenosine stimulation, and that differential importance of the individual isoenzymes depends on cellular cyclic AMP levels.

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Section: Introductionmentioning

confidence: 99%

Role of phosphodiesterase isoenzymes in regulating intracellular cyclic AMP in adenosine-stimulated smooth muscle cells

Xiong

Westhead

Slakey

1995

Biochemical Journal

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Hemodynamic and neuroendocrine response to acute administration of the phosphodiesterase inhibitor BM 14.478 in patients with congestive heart failure

Rauch¹,

Zimmermann²,

Kapp³

et al. 1991

Clinical Cardiology

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: The benzimidazol analogue BM 14.478 is a phosphodiesterase inhibitor with both vasodilator and positive inotropic properties. Hemodynamic parameters and plasma hormone levels of 8 patients (1 female, 7 male) with chronic congestive heart failure NYHA Classes II‐IV (1 patient with coronary artery disease, 7 patients with primary dilated cardiomyopathy) were assessed before and until 6 h after the intravenous application of 1.0 mg BM 14.478. There was a significant decrease of mean pulmonary artery pressure (28±11 vs. 23±11 mmHg; p>0.05), mean right atrial pressure (8.6±5.2 vs. 5.0±4.7 mmHg; p>0.02), and systemic vascular resistance (1651±484 vs. 1206±252 dynes$$s$$cm–5; p>0.05) as early as 10 min after injection of BM 14.478. Pulmonary vascular resistance also was reduced (128±86 vs. 61±39 dynes$$s$$cm–5, 30 min after injection; p>0.02). Simultaneously there was a significant increase of cardiac index (2.3±0.7 vs. 3.1±0.8 1$$min–5$$m–2, 10 min after injection; p>0.02), and stroke volume index (28.8±11.7 vs. 33.9±8.5 ml$$min–1$$m–2; 30 min after injection; p>0.05). Although mean heart rate did not change significantly, some patients reacted with a transient increase. There was also a slight but insignificant increase of the double product. No serious side effects were observed. The hemodynamic improvement was followed by a delayed reduction of plasma levels of epinephrine (51±20 vs. 41±21 pg/ml; p>0.02; 30 min after injection) and atrial natriuretic peptide (229±283 vs. 121±168 pg/ml; p>0.05; 1 h after injection). Mean levels of plasma norepinephrine, however, did not change significantly and individual responses showed large variations, which could not be predicted by the behavior of the hemodynamic parameters. Three of eight patients (2 of these with elevated baseline filling pressures) even showed a marked increase of plasma norepinephrine levels after BM 14.478. Response of plasma renin activity and plasma vasopressin levels to BM 14.478 also was heterogeneous. According to the results of this study, acute administration of the phosphodiesterase inhibitor BM 14.478 has an immediate beneficial hemodynamic effect in patients with severe congestive heart failure by reducing both preload and afterload, and by increasing cardiac index and stroke volume. However, this improvement of hemodynamic parameters is not necessarily accompanied by a favorable short‐term response of plasma hormones, and therefore does not allow any conclusions on survival of these patients.

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Pharmacology of bipyridine phosphodiesterase III inhibitors

Honerjäger¹

1991

American Heart Journal

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Involvement of Cyclic AMP in Vasodilatation by Amrinone: A Comparative Study with 3-Isobutyl-1-Methyl-Xanthine (IBMX)

Cited by 3 publications

References 24 publications

Role of phosphodiesterase isoenzymes in regulating intracellular cyclic AMP in adenosine-stimulated smooth muscle cells

Role of phosphodiesterase isoenzymes in regulating intracellular cyclic AMP in adenosine-stimulated smooth muscle cells

Hemodynamic and neuroendocrine response to acute administration of the phosphodiesterase inhibitor BM 14.478 in patients with congestive heart failure

Pharmacology of bipyridine phosphodiesterase III inhibitors

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