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

1. The circulating cardiac hormones atrial natriuretic peptide (ANP) and br ain natriuretic peptide (BNP) have similar bioactivity, as judged by compar ative short-term studies. However, no study has reported the effects of lon ger-term administration of BNP. Accordingly, we have compared the haemodyna mic, hormonal and renal actions of chronic (4-day) administration of BNP an d ANP (0.5 pmol.min(-1).kg(-1)) in a vehicle-controlled study in normal con scious 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). B NP 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 i nduced a smaller increment in plasma ANP levels (2 pmol/l, P = 0.03) with q ualitatively similar but statistically non-significant changes in plasma cy clic GMP and haemodynamic indices. 3, In conclusion, chronic low-dose infusions of BNP elevate plasma cyclic G MP 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.