Local cardiac responses — Alternative methods of control

Abstract

Much attention has been paid to the influence of the β-adrenoceptor system on cardiac function in heart failure. Full agonists and partial agonists acting on cardiac β 1 receptors have been widely investigated, as has the density of these receptors in the failing heart. However, other cardiac control mechanisms may play important roles in the normal heart as well as in heart failure. The Frank-Starling mechanism of enhanced cardiac contraction produced by mechanical stretching of the ventricular myofibrils is well known. When treating patients with heart failure with diuretics, vasodilators and other drugs that Influence preload, H is important to consider their overal effects in relation to the Starling curves. Atrial stretching also produces compensatory responses which are currently being Intensively studied. Reflex release of atrial natriuretic actor after stimulation of atrial receptors has important physiologic effects in heart failure. The atria, but not the ventricles, are innervated by the vagus; the influence of the parasympathetic nervous system on the heart and circulation is often overlooked. The initial increase in heart rate during exercise is primarily due to withdrawal of vagal influence. Besides acetykholine, the parasympathetic transmitter, many other local hormones may affect cardiac function; these Include prostaglandins, 5-hydroxytryptamine and histamine. Although the activity of the sympathetic nervous system is mediated primarily through β 1 adrenoceptors, both β 2 and α receptors are also found in the heart. Myocardial α 1 receptors, which mediate a positive inotropic effect, have been identified, and prejunctional α 2 receptors may mediate inhibition of norepinephrine release from sympathetic nerves. Cardiac β 2 receptors are believed not to be innervated, but represent hormonal adrenoceptors that are responsive to circulating adrenaline and exogenous stimulation. The importance of many of these non- β 1-receptor cardiac control mechanisms is little known, but further pharmacologic work is continuing which may elucidate their role in both the normal and failing heart.