Rat brain natriuretic peptide is localized in atrial granules and released into the circulation

Abstract

Rat brain natriuretic peptide (BNP) was detected by radioimmunoassay in heart atria and ventricles and in plasma. We have investigated its localization in atria and the possibility of cosecretion of atrial natriuretic factor (ANF) and BNP into the circulation. BNP was detected by chromatographic analysis and immunoblotting in the isolated atrial granules together with ANF: It consisted of two immunoreactive proteins of 14,000 and 2,500 apparent molecular weight. By immunohistochemical methods, BNP was particularly found in the perinuclear region of atrial cardiocytes. Double-labeling immunocytochemical methods colocalized BNP and ANF in the same atrial secretory granules. Basal plasma BNP levels ranged from 2.6 to 4.4 fmol/ml. After stimuli by morphine injection or an aortocaval shunt, BNP levels increased by 4- and 7-fold, respectively, whereas ANF levels rose by 50- and 6-fold, respectively. Depending on the stimulus, BNP release into the circulation is not necessarily proportional to ANF, indicating that BNP may originate not only from the atrial granules but also from other tissues such as the ventricles. These results suggest that BNP may participate with ANF in blood pressure control and salt and water homeostasis.

Altered regulation of natriuretic peptides in the rat heart by prenatal exposure to morphine

“…In contrast, morphine did not alter ANF mRNA in ventricles, but increased it in atria. These findings are consistent with acute studies in which morphine resulted in a 50-fold increase in plasma ANF within 2-120 min, and a 4-fold increase in plasma BNP within 15-45 min (Thibault et al 1992). The mechanisms involved in increasing ANF include massive secretion from atrial stores.…”

“…The mechanisms involved in increasing ANF include massive secretion from atrial stores. The release of BNP did not parallel that of ANF, indicating that BNP originated not only from the atrial granules, but also from other tissues such as the ventricles (Thibault et al 1992). There is a consensus that the most important stimulus for ANF release is activation of stretch receptors within the cardiac atria.…”

“…In adult rats, BNP is co-secreted, in part, with ANF from atrial granules after stimulation with morphine (Thibault et al 1992). Two types of granules have been reported: type I which contains ANF alone, and type II, which contains both ANF and BNP (Hasegawa et al 1991).…”

“…In addition, basal levels of ANF are partially inhibited by naloxone, which implicates endogenous opioids in ANF regulation (Gutkowska et al 1986). Morphine also stimulates BNP release, but to a lesser degree (Aburaya, Suzuki, Minamino, Kanagwa, Tanaka & Matsuo, 1991;Thibault, Charbonneau, Bilodeau, Schiffrin & Garcia, 1992). The mechanisms by which morphine increases ANF and BNP have not yet been elucidated, but it appears that the regulation of ANF is mediated, at least in part, by opioid receptors, without a concomitant rise in blood pressure (Gutkowska, Strick, Pan & McCann, 1993).…”

Usefulness of the brain natriuretic peptide to atrial natriuretic peptide ratio in determining the severity of mitral regurgitation

“…Although the kinetics of atrial-derived BNP in heart failure are not fully known, some studies (23)(24)(25) propose that the atrium is the major source of secretion in the early stage of lowered cardiac function, and that BNP levels from the ventricle increase after the progression to heart failure. BNP and ANP are structurally similar, and BNP is probably also stored in secretion granules (16,33). Therefore, in chronic atrial fibrillation, it is likely that BNP secretion also decreases due to degeneration or atrophy and fibrosis of the atrial muscle, similar to ANP.…”