Authors: Matsumoto, Takayuki; Kobayashi, Tsuneo; Kamata, Katsuo

Source: Current Cardiology Reviews, Volume 2, Number 3, August 2006 , pp. 185-191(7)

Publisher: Bentham Science Publishers

Abstract:

Vascular alterations in diabetes cause or contribute to the etiology of microvascular complications such as nephropathy, neuropathy, and retinopathy. The endothelium controls the vascular smooth muscle tone through the production of vasodilator mediators such as nitric oxide, prostacyclin, and a still-elusive endothelium-derived hyperpolarizing factor (EDHF). Although EDHF is a prominent vasodilator, particularly in smaller arteries, little attention has been paid to the potential role of EDHF responses in diabetes. EDHF function may involve the participation of mediators, including several diffusible factors and non-diffusible factors, (e.g., conduction of hyperpolarization via myoendothelial gap junctions). Indeed, in several vessels, cyclic adenosine 3',5'-monophosphate (cAMP) facilitates EDHF responses by enhancing electrotonic conduction via gap junctions. It has been demonstrated that the alterations in EDHF relaxation seen in mesenteric arteries from diabetic rats may be attributable to an increase in phosphodiesterase3 (PDE3) activity, leading to a reduction in the action of cAMP, and moreover the activity of protein kinase A (PKA) is decreased in such arteries. Although an improvement in EDHF responses has not been, as yet, the subject of any direct pharmaceutical effort, increasing cAMP/PKA signaling (e.g., by inhibiting PDE3 activity) has potential as an interesting therapeutic target in diabetic microvascular disease.

Keywords: EDHF; cAMP; diabetes; phosphodiesterase3; cilostazol; gap junction

Document Type: Research article

DOI: http://dx.doi.org/10.2174/157340306778019405

Affiliations: 1: Department of Physiology and Morphology, Institute of Medicinal Chemistry, Hoshi University, Shinagawa- ku, Tokyo 142-8501, Japan.

Publication date: 2006-08-01

More about this publication?

• Current Cardiology Reviews publishes frontier reviews on all the latest advances on the practical and clinical approach to the diagnosis and treatment of cardiovascular disease. All relevant areas are covered by the journal including arrhythmia, congestive heart failure, cardiomyopathy, congenital heart disease, drugs, methodology, pacing, and preventive cardiology. The journal's aim is to publish the highest quality review articles dedicated to clinical research in the field. The journal is essential reading for all researchers and clinicians in cardiology.

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