Cardiovascular cyclic nucleotide phosphodiesterases and their role in regulating cardiovascular function
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.
Key wordsPDE isozymes cardiac and vascular smooth muscle PDE inhibitors EDRF ANP
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- 2.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 21–48Google Scholar
- 3.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 1–38Google Scholar
- 5.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): A1592Google Scholar
- 11.E. D. Pagani et al.: Cardiovascular cyclic nucleotide phosphodiesterasesGoogle Scholar
- 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: 189–197Google Scholar
- 14.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: A1040Google Scholar
- 16.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: 145–158Google Scholar
- 17.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 133–141Google Scholar
- 18.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): A366Google Scholar
- 20.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: 13–25Google Scholar
- 22.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–Fl224Google Scholar