Do human cardiac beta-2 adrenoceptors play a (patho)physiological role in regulation of heart rate and/or contractility?

There can be no doubt that in human heart in addition to beta 1-adrenoceptors, functional beta 2-adrenoceptors exist. Their (patho)physiological role in regulating heart rate and/or contractility, however, is still an open question. Under normal physiological conditions cardiac beta 2-adrenoceptors may not be of functional importance, since heart rate and contractility seem to be under the control of noradrenaline that in the human heart acts nearly exclusively at beta 1-adrenoceptors. However, in situations of stress when large amounts of adrenaline are released from the adrenal medulla additional stimulation of cardiac beta 2-adrenoceptors may contribute to increases in heart rate and/or contractility. Moreover, in endstage congestive cardiomyopathy where cardiac beta 1-adrenoceptors are selectively down-regulated, cardiac beta 2-adrenoceptors may substitute for the loss of beta 1-adrenoceptors to maintain (at least partially) contractility; under these conditions beta 2-adrenoceptor agonists, like dopexamine, may be of beneficial therapeutic effect. While a decrease in cardiac beta-adrenoceptor function appears to be a general phenomenon in all kinds of heart failure, it is not always due to a selective reduction in cardiac beta 1-adrenoceptors: in mitral valve disease both cardiac beta 1- and beta 2-adrenoceptors decline concomitantly in relation to the degree of heart failure. It is, therefore, doubtful whether under these conditions beta 2-adrenoceptor agonists may also be useful to support the failing heart.