DIFFERING METABOLISM AND BIOACTIVITY OF ATRIAL AND BRAIN NATRIURETIC PEPTIDES IN ESSENTIAL-HYPERTENSION

Plasma concentrations of both atrial natriuretic peptide (ANP) and bra in natriuretic peptide (BNP) are elevated in severe hypertension, acut e myocardial infarction, and heart failure. In the current study of in dividuals with essential hypertension, we have documented the hemodyna mic, hormonal, and endocrine effects of infusions of these two peptide s given alone or in combination in equimolar doses calculated to induc e increments in plasma peptides to concentrations (30 to 60 pmol/L) ob served in these disease states. The metabolic clearance rate of ANP (4 .56+/-0.62 Limin) was greater than that for BNP (3.4+/-0.23 L/min, P<. 001). Infusions of each cardiac hormone impaired the clearance of coin fused peptide. All peptide infusions enhanced natriuresis (17% to 70% above preinfusion levels versus placebo, 6%; P<.001), lowered blood pr essure (10 to 18 mm HS fall in mean arterial pressure below placebo le vels, P<.001), increased hematocrit, suppressed the renin-angiotensin- aldosterone system, and enhanced plasma norepinephrine concentrations. The natriuretic and blood pressure-lowering effects of BNP were twofo ld to threefold those of ANP. In contrast, ANP-induced increments in p lasma and urinary second messenger (cGMP) levels were greater than tho se for BNP. Both peptides suppressed the renin-angioten sin-aldosteron e system (approximately one-third fall in renin activity and plasma al dosterone) and enhanced plasma norepinephrine concentrations (+30%) to a similar degree. Increments in plasma ANP and BNP that occur simulta neously in cardiovascular disease states appear capable of causing hem odynamic, endocrine, and renal effects that would tend to ameliorate c onditions such as hypertension or heart failure.