Summary
We have described five phosphodiesterase (PDE) isozymes that can be found in cardiac and vascular smooth muscle of animals and humans. Much of the evidence for the role that these isozymes have in the regulation of cellular processes has been generated through, or awaits, the identification of selective and potent PDE inhibitors. While selective inhibitors of the cGMP-inhibitable (cGi)-PDE isozyme have been approved for use in the acute treatment of heart failure, selective inhibitors of the cGMP-PDE have not been extensively explored as potential candidates for the treatment of cardiovascular diseases. More potent selective inhibitors of the cGMP-PDE isozyme are needed to determine whether these pharmacological potentiators of EDRF and ANP will be useful in the therapy of angina, hypertension or heart failure.
This is a preview of subscription content, log in via an institution.
Buying options
Tax calculation will be finalised at checkout
Purchases are for personal use only
Learn about institutional subscriptionsPreview
Unable to display preview. Download preview PDF.
References
Alousi AA, Stankus GP, Stuart JC, Walton LH (1983) Characterization of the cardiotonic effects of milrinone, a new and potent cardiac bipyridine, on isolated tissues from several animal species. J Cardiovasc Pharmacol 5: 804–811
Alousi AA, Canter JM, Cicero F, Fort DJ, Helstosky A, Lesher GY, Montenaro MJ, Stankus GP, Stuart JC, Walton LH (1984) Pharmacology of milrinone. In: Braunwald E, Sonnenblick EH, Chakrin LW, Schwarz Jr. RP (eds) Milrinone Investigation of New Inotropic Therapy for Congestive Heart Failure. Raven Press, New York, pp 21–48
Beavo JA (1988) Multiple isozymes of cyclic nucleotide phosphodiesterases. In: Greengard P, Robinson GA (eds) Advances in Second Messenger and Phosphoprotein Research, Vol 22. Raven Press, New York, pp 1–38
Beavo JA, Reifsnyder DH (1990) Primary sequence of cyclic nucleotide phosphodiesterase isozymes and the design of selective inhibitors. Trends Pharmacol Sci 11: 150–155
Bode DC, Pagani ED, O’Connor B, Silver PJ (1991) Potentiation of cGMP accumulation in renal cells by inhibition of cGMP phosphodiesterase (PDE). FASEB J 5 (6): A1592
Böhm D, Diet F, Erdman E (1988) Enhancement of the effectiveness of milrinone to increase force of contraction by stimulation of cardiac beta adrenoceptors in the failing human heart. Klin Wochenschr 66: 957–962
Coquil J-F, Franks DJ, Wells JN, Dupuis M, Hamet P (1980) Characteristics of a new binding protein distinct from the kinase for guanosine 3’:5’-monophosphate in rat platelets. Biochim Biophy Acta 631: 148–165
Danielson W, V der Leyen H, Meyer W, Neumann J, Schmitz W, Scholz H, Starbatty J. Stein B, Doring V, Kalmer P (1989) Basal and isoprenaline-stimulated cAMP content in failing versus nonfailing human cardiac preparations. J Cardiovasc Pharmacol 14: 171–173
De Felice AF, Harris AL, Frering R, Horan P (1989) Beneficial hemodynamic effects of milrinone and enalapril in conscious rats with healed myocardial infarction. Eur J Pharmacol 167: 211–220
Dundore RL, Pratt PF, O’Connor B, Buchholz RA, Pagani ED (1991) Nw-nitro-L-arginine attenuates the accumulation of aortic cyclic GMP and the hypotension produced by zaprinast. Eur J Pharmacol 200: 83–87
E. D. Pagani et al.: Cardiovascular cyclic nucleotide phosphodiesterases
Feldman AM, Cates AE, Veazcy WB, Hershberger RE, Bristow MR, Baughman KL, Baumgartner WA, Dop CV (1988) Increase of the 40,000-mol wt pertussis toxin substrate ( G protein) in the failing human heart. J Clin Invest 82: 189–197
Feldman MD, Copelas L, Gwathmey JK, Philips P, Warren SE, Schoen FJ, Grossman W, Morgan JP (1987) Deficient production of cyclic AMP: pharmacologic evidence of an important cause of contractile dysfunction in patients with end-stage heart failure. Circ 75: 311–339
Francis S, Lincoln TM, Corbin JD (1980) Characterization of a novel cGMP binding protein from rat lung. J Biol Chem 255: 620–626
Harris AL, VanAller G, DeFelice AF, Horan PJ, Frering R, Pagani E, Silver P (1989) Effect of milrinone on isolated papillary muscles from 10 week myocardially-infarcted ( MI) and sham-operated rats. FASEB J 3: A1040
Ishii K, Chang B, Kerwin JF, Huang ZJ, Murad F (1990) Nw-nitro-L-arginine: a potent inhibitor of endothelium-derived relaxing factor formation. Eur J Pharmacol 176: 219–223
Lee KC, Canniff PC, Hamel DW, Pagani ED, Ezrin AM (1991) Cardiovascular and renal effects of milrinone in beta-adrenoreceptor blocked and non-blocked anesthetized dogs. Drugs Under Exp Clin Res 3: 145–158
LeJemtel TH, Maskin CS, Chadwick B, Sonnenblick EH (1984) Hemodynamic effects of intravenous and oral milrinone in patients with chronic heart failure. In: Braunwald E, Sonnenblick EH, Chakrin LW, Schwarz Jr. RP (eds) Milrinone Investigation of New Inotropic Therapy for Congestive Heart Failure. Raven Press, New York, pp 133–141
Pagani E, Fort DJ, Ezrin AM, Silver PJ (1988) In vitro cardiovascular phosphodiesterase inhibition and in vivo cardiovascular activity of milrinone in dogs. Fed Proc 2 (4): A366
Pfeffer MA, Pfeffer JM, Steinberg BS, Finn P (1985) Survival after an experimental myocardial infarction: beneficial effects of long-term Captopril therapy. Circ 72: 406–412
Silver PJ, Allen P, Etzler J, Hamel L, Bentley RG, Pagani ED (1990) Cellular distribution and pharmacological sensitivity of low Km cyclic nucleotide phosphodiesterase isozymes in human cardiac muscle from normal and cardiomyopathic subjects. Sec Mes Phospho 13: 13–25
Sweet CS, Ludden CT, Stabilito II, Emmert SE, Heyse IF (1988) Beneficial effects of milrinone and enalapril on long-term survival of rats with healed myocardial infarction. Eur J Pharmacol 147: 29–37
Wong XR, Xie MH, Shi LB, Liu FY, Huang CL, Gardner DG, Cogan MG (1988) Urinary cGMP as biological marker of the renal activity of atrial natriuretic factor. Amer J Physiol 255: Fl220–Fl224
Zemelman BV, Chu SW, Walker WA (1989) Host response to escherichia coli heat-liable enterotoxin via two microvilli membrane receptors in the rat intestine. Infection and Immunity 57: 2947–2952
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 1992 Dr. Dietrich Steinkopff Verlag GmbH & Co.KG, Darmstadt
About this paper
Cite this paper
Pagani, E.D., Buchholz, R.A., Silver, P.J. (1992). Cardiovascular cyclic nucleotide phosphodiesterases and their role in regulating cardiovascular function. In: Hasenfuss, G., Holubarsch, C., Just, H., Alpert, N.R. (eds) Cellular and Molecular Alterations in the Failing Human Heart. Steinkopff. https://doi.org/10.1007/978-3-642-72474-9_6
Download citation
DOI: https://doi.org/10.1007/978-3-642-72474-9_6
Publisher Name: Steinkopff
Print ISBN: 978-3-642-72476-3
Online ISBN: 978-3-642-72474-9
eBook Packages: Springer Book Archive