Copyright © 1991 by the European Society of Cardiology.
© 1991 The European Society of Cardiology
The role of alpharadrenergic and muscarinic receptors in cardiac function
Abteilung Allgemeine Pharmakologie, Universitdts-Krankenhaus Eppendorf, MartinistraBe 52,D-W-2000 Hamburg 20,Germany
Correspondence: Prof. Dr. med. Wilhelm Schmitz, Pharmakologisches Institut, Universitäts-Krankenhaus Eppendorf, Universität Hamburg, Martinistraβe 52, D-2000 Hamburg 20, Germany
The positive inotropic effect of an alpha1-adrcnoccptor agonist, such as phenylephrine, is accompanied by an increase in the presumed second messenger, inositol 1,4,5-trisphosphate (1,4,5-IP3) and inositol 1,3,4,5-tetrakisphosphate (1,3,4,5-IP4), which may release calcium from the sarcoplasmic reticulum (SR) and/or facilitate calcium entry from the extracellular space. In addition, phenylephrine sensitizes the contractile proteins for calcium. Alpha1-adrenergic positive inotropic effects are enhanced in heart muscle preparations from cardio-myopathic hamsters and are reduced in heart muscle preparations from human failing myocardium.
How the negative inotropic effects of M-cholinoceptor agonists work in the presence of cAMP-increasing agents in ventricular heart muscle preparations is discussed. It involves cAMP-reduction, an increase in cGMP and activation of phosphatase activity. In a rat model, chronic beta-adrenergic stimulation leads to increased sensitivity of rat ventricular tissue for the negative inotropic effect of the M-cholinoceptor agonist, carbachol. This might be due to facilitated signal transduction via increased G1 proteins. In human ventricular tissue from hearts with end-stage heart failure, due to idiopathic dilated cardiomyopathy (IDC), an increased G1 protein has also been found. However, the negative inotropic effects of carbachol were unchanged. The data indicate that changes in alpha-adrenergic and M-cholinergic responses in the heart may depend on underlying causes that induce changes.
Key Words: Alpha1-adrenoceptors M-cholinoceptors positive inotropic effects negative inotropic effects G proteins failing heart