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BNP was discovered in the porcine brain extract in 1988. Subsequent studies have demonstrated that BNP is a cardiac hormone in humans. Plasma level of BNP is increased in patients with heart failure more than ANP. Therefore, BNP measurements as a biomarker for heart failure spread all over our country and all over the world. Now the guideline in the world recognizes that BNP is a useful biomarker for diagnosis for acute and chronic heart failure. However, the usefulness of "BNP-guided therapy for heart failure" is still controversial at present, because randomized-controlled studies have shown the neutral results. Although more than twenty years have passed since its discovery, recent studies have shown the new findings in BNP research. I describe here the recent advance of BNP research.

The natriuretic peptide comprises at least three ligands(ANP, BNP, and CNP) and three receptors(GC-A, GC-B, and Clearance receptor). ANP and BNP are cardiac hormones, which regulate blood pressure and body fluid volume. Angiotensin II, the effector peptide of the renin-angiotensin system, regulates cellular growth in response to developmental, physiological and pathological processes. Recently, evidences suggest that cardiovascular homeostasis is determined by the balance between these two important counter-regulatory pathways. In this paper, we will discuss the molecular mechanism of the cross-talk between the two systems, including our recent findings using the mice deficient for GC-A and angiotensin II receptors. The results suggest that the endogenous natriuretic peptide system inhibits the cardiac angiotensin system and protects the heart from excessive pathological remodelings.

The literature review reflects new aspects of humoral regulation in hypertension and target-organ damages with special regard to natriuretic peptide system(NPS) and adrenomedullin(AM). NPS and AM are recently discovered regulators which serve as antihypertensive and target-organ protective factors. These peptides have both diuretic and natriuretic properties and a relaxing effect on the vasculature. Moreover, they antagonize the proliferative and hypertrophic stimuli in the vasculature and heart. Recently, progressive technics of molecular biology clearly revealed crucial roles of these peptides for cardiovascular regulation in both normal and pathological states including hypertension and related organ damages. Natriuretic peptides, potentially AM, are new therapeutic tools for heart failure and main targets for further development of new antihypertensive drugs such as vasopeptidase inhibitor.