Copyright © 2007, European Society of Cardiology
Phosphodiesterase regulation of nitric oxide signaling
Division of Cardiology, Department of Medicine, Johns Hopkins Medical Institutions, Baltimore, Maryland, United States
* Corresponding author. Ross 835, Johns Hopkins Medical Institutions, 720 Rutland Avenue, Baltimore, 21205 Maryland, United States. Tel.: +1 410 955 7153; fax: +1 410 502 2558. dkass{at}jhmi.edu
Nitric oxide regulation of the cardiovascular system involves both cGMP-dependent and independent mechanisms. The former directly interacts with the family of catabolic phosphodiesterases (PDEs) that control cGMP levels and thus distal effects such as protein kinase G stimulation. Growing evidence supports an important role of several PDEs, including PDE1, PDE2, and PDE5, in the regulation of cGMP in both vascular smooth muscle and cardiac myocytes. These PDEs have relatively little impact on resting function, but they can potently modulate acute contractile tone in cells stimulated by external agonists such as angiotensin or catecholamines. Regulation by PDEs is compartmentalized, with selective interactions occurring between a given source of cGMP and PDE hydrolysis. PDE1 and/or PDE5 are also reportedly up-regulated in chronic disease conditions such as atherosclerosis or cardiac pressure-load stress and heart failure as well as in response to long-term exposure to nitrates. Such up-regulation is thought to contribute to vascular and cardiac pathophysiology and to drug tolerance. Recent studies utilizing selective PDE5 inhibitors support significant cross-signaling with NO–cGMP synthetic pathways that may be particularly helpful in treating certain disease states.
KEYWORDS Cyclic nucleotides; Protein kinase G; cGMP; Sildenafil; Heart function
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  J. L. Sartoretto, B. Y. Jin, M. Bauer, F. B. Gertler, R. Liao, and T. Michel Regulation of VASP phosphorylation in cardiac myocytes: differential regulation by cyclic nucleotides and modulation of protein expression in diabetic and hypertrophic heart Am J Physiol Heart Circ Physiol, November 1, 2009; 297(5): H1697 - H1710. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. J. Pearce, J. M. Williams, C. R. White, and T. M. Lincoln Effects of chronic hypoxia on soluble guanylate cyclase activity in fetal and adult ovine cerebral arteries J Appl Physiol, July 1, 2009; 107(1): 192 - 199. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. S. Weiss, H. C. Champion, J. A. Williams, W. A. Baumgartner, and A. S. Shah Long-acting oral phosphodiesterase inhibition preconditions against reperfusion injury in an experimental lung transplantation model. J. Thorac. Cardiovasc. Surg., May 1, 2009; 137(5): 1249 - 1257. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. T. Demchenko, A. Ruehle, B. W. Allen, R. D. Vann, and C. A. Piantadosi Phosphodiesterase-5 inhibitors oppose hyperoxic vasoconstriction and accelerate seizure development in rats exposed to hyperbaric oxygen J Appl Physiol, April 1, 2009; 106(4): 1234 - 1242. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Hsu, T. Nagayama, N. Koitabashi, M. Zhang, L. Zhou, D. Bedja, K. L. Gabrielson, J. D. Molkentin, D. A. Kass, and E. Takimoto Phosphodiesterase 5 inhibition blocks pressure overload-induced cardiac hypertrophy independent of the calcineurin pathway Cardiovasc Res, February 1, 2009; 81(2): 301 - 309. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Pokreisz, S. Vandenwijngaert, V. Bito, A. Van den Bergh, I. Lenaerts, C. Busch, G. Marsboom, O. Gheysens, P. Vermeersch, L. Biesmans, et al. Ventricular Phosphodiesterase-5 Expression Is Increased in Patients With Advanced Heart Failure and Contributes to Adverse Ventricular Remodeling After Myocardial Infarction in Mice Circulation, January 27, 2009; 119(3): 408 - 416. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Nagayama, S. Hsu, M. Zhang, N. Koitabashi, D. Bedja, K. L. Gabrielson, E. Takimoto, and D. A. Kass Sildenafil stops progressive chamber, cellular, and molecular remodeling and improves calcium handling and function in hearts with pre-existing advanced hypertrophy caused by pressure overload. J. Am. Coll. Cardiol., January 13, 2009; 53(2): 207 - 215. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Kruger, S. Kotter, A. Grutzner, P. Lang, C. Andresen, M. M. Redfield, E. Butt, C. G. dos Remedios, and W. A. Linke Protein Kinase G Modulates Human Myocardial Passive Stiffness by Phosphorylation of the Titin Springs Circ. Res., January 2, 2009; 104(1): 87 - 94. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Nagayama, M. Zhang, S. Hsu, E. Takimoto, and D. A. Kass Sustained Soluble Guanylate Cyclase Stimulation Offsets Nitric-Oxide Synthase Inhibition to Restore Acute Cardiac Modulation by Sildenafil J. Pharmacol. Exp. Ther., August 1, 2008; 326(2): 380 - 387. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. R. Wilkins, J. Wharton, F. Grimminger, and H. A. Ghofrani Phosphodiesterase inhibitors for the treatment of pulmonary hypertension Eur. Respir. J., July 1, 2008; 32(1): 198 - 209. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. W. M. Nausch, J. Ledoux, A. D. Bonev, M. T. Nelson, and W. R. Dostmann Differential patterning of cGMP in vascular smooth muscle cells revealed by single GFP-linked biosensors PNAS, January 8, 2008; 105(1): 365 - 370. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. A. Kass, H. C. Champion, and J. A. Beavo Phosphodiesterase Type 5: Expanding Roles in Cardiovascular Regulation Circ. Res., November 26, 2007; 101(11): 1084 - 1095. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Lamas, C. J. Lowenstein, and T. Michel Nitric oxide signaling comes of age: 20 years and thriving Cardiovasc Res, July 15, 2007; 75(2): 207 - 209. [Full Text] [PDF]
|
|