Chronic infusions of brain natriuretic peptide in conscious sheep: bioactivity at low physiological levels

1. The circulating cardiac hormones atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) have similar bioactivity, as judged by comparative short-term studies. However, no study has reported the effects of longer-term administration of BNP. Accordingly, we have compared the haemodynamic, hormonal and renal actions of chronic (4-day) administration of BNP and ANP (0.5 pmol. min-1.kg-1) in a vehicle-controlled study in normal conscious sheep. 2.BNP infusions raised plasma BNP levels within the physiological range (4 pmol/l increment, P<0.001) and increased cyclic GMP levels (P=0.01). BNP infusions induced significant falls in right atrial pressure (P=0.048), stroke volume (P=0.014) and cardiac output (P=0. 003) associated with a rise in haematocrit (P=0.001). There were no significant renal effects or changes in renin-aldosterone. By comparison, equimolar infusion of ANP induced a smaller increment in plasma ANP levels (2 pmol/l, P=0.03) with qualitatively similar but statistically non-significant changes in plasma cyclic GMP and haemodynamic indices.3.In conclusion, chronic low-dose infusions of BNP elevate plasma cyclic GMP levels and induce significant haemodynamic actions. This study provides evidence that subtle variations in circulating BNP levels, well within the physiological range, may be important in long-term cardiovascular control.