We conclude that (1) BNP is secreted mainly from the left ventricle in normal adult humans as well as in patients with left ventricular dysfunction, whereas ANP is secreted from atria in normal adult humans and also from the left ventricle in patients with left ventricular dysfunction; (2) secretion of BNP as well as ANP from the left ventricle increases in proportion to the severity of the left ventricular dysfunction, suggesting that the secretions of ANP and BNP from the left ventricle are regulated mainly by wall tension of the left ventricle; and (3) the peripheral plasma levels of ANP and BNP reflect the secretion rate of these hormones from the left ventricle and may be used as a marker of the degree of left ventricular dysfunction in patients with left ventricular dysfunction.

IntroductionUsing a specific radioimmunoassay for human brain natriuretic peptide (hBNP) with a monoclonal antibody, we have investigated its synthesis, secretion, and clearance in comparison with those of atrial natriuretic peptide (ANP) in normal subjects and patients with congestive heart failure (CHF Since the discovery of atrial natriuretic peptide (ANP)' in the heart (1-5) and subsequently in the brain (5-10), ANP has been implicated in body fluid homeostasis and blood pressure control as a hormone and as a neuropeptide ( 1-1 1). We and others have previously demonstrated that the synthesis and secretion of ANP in the heart are increased in patients with congestive heart failure (CHF) in relation to its severity (12-18).More recently, brain natriuretic peptide (BNP) was isolated from the porcine brain (19), which has either 26 or 32 amino acid residues, porcine (p) respectively (20), with a remarkable sequence homology to ANP and has peripheral and central actions similar to those of ANP (19,(21)(22)(23). BNP is also synthesized in, and secreted into the circulation from, the porcine heart (24, 25). Subsequently, we and others isolated rat BNP (rBNP) with 45 amino acid residues from the rat heart (26-28). To date, however, the information on BNP in humans is scarce, mainly for lack ofcross-reactivity of human BNP (hBNP) with antisera against pBNP or rBNP.Recently

Background-Coronary spasm plays an important role in the pathogenesis of ischemic heart diseases in general. However, the precise mechanism(s) responsible for coronary spasm remains to be elucidated, and we examined the molecular genetics of coronary spasm. Methods and Results-We searched for the possible mutations in the endothelial nitric oxide synthase (eNOS) gene in patients with coronary spasm. In this study, we demonstrate the existence of 3 linked mutations in the 5Ј-flanking region of the eNOS gene (T

Hyperglycemia in response to oral glucose loading rapidly suppresses endothelium-dependent vasodilation, probably through increased production of oxygen-derived free radicals. These findings strongly suggest that prolonged and repeated post-prandial hyperglycemia may play an important role in the development and progression of atherosclerosis.