Affiliation:
1. Scienze Mediche, Università degli Studi di Brescia (Italy) (M.C.), and Klinik III für Innere Medizin der Universität zu Köln (Germany) (M.B.).
Abstract
Hypertension-induced cardiac hypertrophy is a predictor of the development of cardiac failure. It is unknown which cellular markers contribute to the progression from compensated hypertrophy to failure. In heart failure, several signal transduction defects leading to adenylate cyclase desensitization have been demonstrated, such as β-adrenoceptor downregulation, increase of inhibitory G protein expression, and uncoupling of β-adrenergic receptors, presumably by an increase of receptor kinase activity. In hypertensive heart disease, most studies have been performed in rat models of hypertension. As in heart failure, heterologous adenylyl cyclase desensitization occurs. The mechanisms are often different between the heterogeneous models for acquired and genetic hypertension, but G
i
protein alterations and β-adrenoceptor downregulation have been observed frequently. The underlying mechanism for desensitization is most likely a sympathetic activation in established hypertension rather than genetic alterations of signal transduction proteins. The data available suggest that β-adrenergic desensitization could represent a mechanism that contributes to the progression from hypertrophy to failure. The key question remains whether those hypertensive patients who develop heart failure are more prone to β-adrenergic desensitization or whether early intervention to reduce sympathetic activity is more effective in preventing or delaying the transition from compensated hypertrophy to overt failure.
Publisher
Ovid Technologies (Wolters Kluwer Health)
Reference52 articles.
1. Schwinn DA Caron MG Lefkowitz RJ. The beta-adrenergic receptor as a model for molecular structure-function relationships in G-protein-coupled receptors. In: Fozzard HA Habes E Jennings RB Katz A Morgan HE eds. The Heart and Cardiovascular System . 2nd ed. New York NY: Raven Press Publishers; 1992:1657-1684.
2. Susanni EE Vatner DE Homcy CJ. Beta-adrenergic receptor/adenylyl cyclase system. In: Fozzard HA Habes E Jennings RB Katz A Morgan HE eds. The Heart and Cardiovascular System . 2nd ed. New York NY: Raven Press Publishers; 1992:1685-1708.
3. β-Adrenergic Inhibition of Cardiac Sodium Channels by Dual G-Protein Pathways
4. Regulation of protein synthesis and degradation in adult ventricular cardiomyocytes
5. Schlüter KD Zhou XJ Piper HM. Trophic coupling to β 2 -adrenoceptor stimulation in adult cardiomyocytes is induced by transforming-growth-factor-β (TGF-β). Pflugers Arch. 1994;426(suppl 6):R117. Abstract.
Cited by
91 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献