LOW-DOSE BRAIN NATRIURETIC PEPTIDE INFUSION IN NORMAL MEN AND THE INFLUENCE OF ENDOPEPTIDASE INHIBITION

1. To assess the threshold dose for bioactivity of brain natriuretic p eptide and the role of endopeptidase 24.11 in metabolism of brain natr iuretic peptide at physiological plasma levels, we studied eight norma l men receiving 2 h infusions of low-dose brain natriuretic peptide [0 .25 and 0.5 pmol min(-1) kg(-1) with and without pretreatment with an endopeptidase inhibitor (SCH 32615, 250 mg intravenously)] in placebo- controlled studies. 2. Plasma brain natriuretic peptide increased 2-fo ld during the infusion of 0.25 pmol min(-1) kg(-1) (mean increment abo ve control 3.9 pmol/l, P < 0.001), and tripled (P < 0.001) with 0.5 pm ol min(-1) kg(-1). Plasma renin activity was inhibited by both doses ( 14.8%, P < 0.01, and 20%, P < 0.001, respectively), A significant natr iuresis (56% increase in urine sodium/creatinine ratio, P < 0.02) occu rred with the higher dose, Blood pressure, haematocrit, plasma cGMP, a trial natriuretic peptide and aldosterone were unaffected by either do se. 3. Compared with brain natriuretic peptide (0.5 pmol min(-1) kg(-1 )) alone, SCH 32615 pretreatment increased peak plasma brain natriuret ic peptide (13.4 +/- 0.78 versus 12.4 +/- 0.86 pmol/l, P < 0.05), ANP (7.5 +/- 0.96 versus 5.9 +/- 0.4 pmol/l, P < 0.01) and cGMP (4.8 +/- 1 .7 versus 3.9 +/- 1.4 nmol/l, P < 0.001). Plasma renin activity was fu rther suppressed with SCH 32615 pretreatment (29% compared with 20%, P < 0.001). 4. Small acute increments in plasma brain natriuretic pepti de (4 pmol/l) have significant biological effects in normal men withou t altering plasma atrial natriuretic peptide or cGMP.