The Cardiac β-Adrenoceptor–Mediated Signaling Pathway and Its Alterations in Hypertensive Heart Disease
- 1 March 1997
- journal article
- review article
- Published by Wolters Kluwer Health in Hypertension
- Vol. 29 (3), 715-722
- https://doi.org/10.1161/01.hyp.29.3.715
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.Keywords
This publication has 31 references indexed in Scilit:
- The Effect of Carvedilol on Morbidity and Mortality in Patients with Chronic Heart FailureNew England Journal of Medicine, 1996
- Beta-adrenergic neuroeffector mechanisms in cardiac hypertrophy of renin transgenic rats.Hypertension, 1994
- Cardiac Norepinephrine, p-Adrenoceptors, and Giα-Proteins in Prehypertensive and Hypertensive Spontaneously Hypertensive RatsJournal of Cardiovascular Pharmacology, 1994
- Enhanced Myocardial Function in Transgenic Mice Overexpressing the β 2 -Adrenergic ReceptorScience, 1994
- Desensitization of adenylate cyclase and increase of Gi alpha in cardiac hypertrophy due to acquired hypertension.Hypertension, 1992
- Epinephrine and the genesis of hypertension.Hypertension, 1992
- Peripheral adrenergic receptors in hypertension.Hypertension, 1990
- β-Adrenergic Inhibition of Cardiac Sodium Channels by Dual G-Protein PathwaysScience, 1989
- Molecular evidence of genetic heterogeneity in Wistar-Kyoto rats: implications for research with the spontaneously hypertensive rat.Hypertension, 1989
- Cloning and characterization of the human gene for the α‐subunit of Gi2, a GTP‐binding signal transduction proteinFEBS Letters, 1988