MECHANICAL AND NEUROENDOCRINE REGULATION OF THE ENDOCRINE HEART

The cardiac natriuretic peptides (NP)-atrial natriuretic factor (ANF) and brain natriuretic peptide (BNP)-are polypeptide hormones produced by cardiocytes in the atria of mammals. ANF and BNP are continuously r eleased from the heart, but appropriate mechanical or neuroendocrine s timuli increase their rate of release with or without a concomitant in crease in synthesis, The results of our investigations lead us to prop ose that the endocrine response of the heart to pressure or volume loa d varies in relation to whether the challenge is acute, subacute or ch ronic. The acute response to stretch is based on a phenomenon referred to as ''stretch-secretion coupling'' which results in enhanced secret ion of NP stored in the atria. NP release following stretch is made at the expense of a depletable NP pool with no apparent effect on synthe sis. The stimulation of NP production that is seen during mineralocort icoid escape is referred to as ''subacute'' and is characterized by st imulation of atrial ANF and BNP gene transcription secondary to volume overload in which plasma ANF, but not plasma BNP, is significantly el evated. With chronic stimulation, as seen in DOCA-salt treatment at th e hypertensive stage, activation of the cardiac fetal program in ventr icle is seen together with a stimulation of ANF and BNP production in both atria and ventricles. However, the activation of NP gene expressi on in the atria is not necessarily associated with fetal isogene expre ssion even though the ventricular hypertrophic process is characterize d by the expression of fetal isogenes, including ANF and BNP, that are normally expressed in the fetal ventricle. It seems likely that the a cute stimulation of NP release is based on an electromechanical coupli ng. However, protracted stimulation of release is seen in situations i n which profound neuroendocrine changes have taken place, thus suggest ing that the primary stimulus for chronically enhanced NP gene express ion and NP release is based on changes in the hormonal environment of the atrial cardiocyte. It is concluded that the endocrine heart respon ds to changes in hemodynamic load with specific changes in translation al, post-translational and storage processes for ANF and BNP following acute or chronic stimulation. As a result, plasma levels of ANF and B NP may be used as indicators of the degree of atrial hemodynamic overl oad and ventricular hypertrophy, respectively. It may be advanced that the endocrine heart differentiates and responds to different hemodyna mic challenges in either acute or chronic conditions with specific cha nges in transcription, translation, post-translational processing, sto rage, and release of ANF and BNP, We propose that this differentiation is part of the reason for the heart to produce two hormones with simi lar spectra of activity. This paradigm warrants further investigation.