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Differing metabolism and bioactivity of atrial and brain natriuretic peptides in essential hypertension
G B Pidgeon1, A M Richards, M G Nicholls
1Department of Medicine, Christchurch School of Medicine, New Zealand.
Insights
Elevated atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) levels in cardiovascular diseases may help lower blood pressure and improve kidney function. These cardiac hormones show potential therapeutic benefits in managing hypertension and heart failure.
Area of Science:
- Cardiovascular Physiology
- Endocrinology
- Nephrology
Background:
- Plasma concentrations of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) are elevated in severe hypertension, acute myocardial infarction, and heart failure.
- Understanding the effects of these natriuretic peptides is crucial for managing cardiovascular diseases.
Purpose of the Study:
- To investigate the hemodynamic, hormonal, and endocrine effects of infusing ANP and BNP, alone and in combination, in individuals with essential hypertension.
- To compare the metabolic clearance rates and physiological effects of ANP and BNP.
Main Methods:
- Infusion of equimolar doses of ANP and BNP to achieve disease-state concentrations (30-60 pmol/L).
- Measurement of hemodynamic parameters, hormonal levels, and renal responses (natriuresis).
- Assessment of metabolic clearance rates and effects on the renin-angiotensin-aldosterone system and norepinephrine.
Main Results:
- Metabolic clearance rate of ANP was greater than BNP; coinfusion impaired clearance of each peptide.
- Both ANP and BNP infusions enhanced natriuresis and lowered blood pressure, with BNP showing 2-3 fold greater effects.
- ANP induced greater increases in cGMP levels, while both peptides similarly suppressed the renin-angiotensin-aldosterone system and increased norepinephrine.
Conclusions:
- Simultaneous increases in ANP and BNP in cardiovascular diseases may exert beneficial hemodynamic, endocrine, and renal effects.
- These natriuretic peptides possess the potential to ameliorate conditions such as hypertension and heart failure.
- BNP demonstrates more potent blood pressure-lowering and natriuretic effects compared to ANP.
Abstract:
Plasma concentrations of both atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) are elevated in severe hypertension, acute myocardial infarction, and heart failure. In the current study of individuals with essential hypertension, we have documented the hemodynamic, hormonal, and endocrine effects of infusions of these two peptides given alone or in combination in equimolar doses calculated to induce increments in plasma peptides to concentrations (30 to 60 pmol/L) observed in these disease states. The metabolic clearance rate of ANP (4.56 +/- 0.62 L/min) was greater than that for BNP (3.4 +/- 0.23 L/min, P <.001). Infusions of each cardiac hormone impaired the clearance of coinfused peptide. All peptide infusions enhanced natriuresis (17% to 70% above preinfusion levels versus placebo, 6%; P <.001), lowered blood pressure (10 to 18 mm Hg fall in mean arterial pressure below placebo levels; 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 twofold to threefold those of ANP. In contrast, ANP-induced increments in plasma and urinary second messenger (cGMP) levels were greater than those for BNP. Both peptides suppressed the renin-angiotensin-aldosterone system (approximately one-third fall in renin activity and plasma aldosterone) and enhanced plasma norepinephrine concentrations (+30%) to a similar degree. Increments in plasma ANP and BNP that occur simultaneously in cardiovascular disease states appear capable of causing hemodynamic, endocrine, and renal effects that would tend to ameliorate conditions such as hypertension or heart failure.