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Abstract

Brain natriuretic peptide (BNP) is a 32-amino-acid peptide of cardiac origin with natriuretic and vasodilatory properties which is currently being developed for the treatment of congestive heart failure (CHF). Dendroaspis natriuretic peptide (DNP) is a recently discovered 38-amino-acid peptide structurally similar to ANP, BNP and CNP with potent natriuretic and vasoactive actions whose immunoreactivity is present in human plasma and elevated in human CHF. Data suggest that DNP is the natriuretic peptide most resistant to degradation by neutral endopeptidase due to its long C-terminus. Based upon the potent biological properties of both peptides we designed and synthesized a chimeric peptide BD-NP which consists of the 26 amino acid ring structure of BNP and the 15 amino acid C-terminus of DNP. We then assessed the cardiorenal actions of synthetic BD-NP in normal dogs in vivo. The therapeutic potential of parenterally administered BD-NP was assessed upon cardiorenal and endocrine function in 6 anesthetized dogs and compared with the placebo control group (n=7) which received saline. Intravenous synthetic BD-NP was infused after baseline measurements at 10 and 50 ng/kg/min. * p<0.05 vs. Baseline.

Administration of low and high dose BD-NP decreased MAP (from baseline 133±6 to 122±4 and 104±3* mmHg), RAP (from 2.8±0.4 to 1.7±0.3* and 1.2±0.3* mmHg), PAP (from 16.7±0.8 to 15.3±0.5 and 12.4±0.4* mmHg) and PCWP (from 5.2±0.5 to 3.5±0.5* and 1.8±0.4* mmHg). BD-NP increased GFR (from 31±3 to 46±5* and 46±4* ml/min) without changes in RBF. BD-NP enhanced natriuresis (UNaV from 14.8±10 to 121.8±52* and 158.8±57* μEq/min) and diuresis (UV from 0.27±0.1 to 1.25±0.3* and 2.22±0.5* ml/min) with a decrease in proximal fractional reabsorption of sodium (from 83.8±5.0 to 68.6±3.8* and 61.7±3.8* %). Both doses of BD-NP decreased plasma renin activity (from 8.7±1.0 to 4.1±0.6* and 5.8±1.0* ng/ml/hr). In contrast, all parameters were unchanged with placebo.

We report that this new designer peptide BD-NP potently lowers blood pressure, reduces cardiac filling pressures, increases glomerular filtration rate, augments natriuresis and diuresis and possesses renin-suppressing properties. These findings support a possible therapeutic role for this new designer peptide in the treatment of cardiovascular diseases such as hypertensive crisis and acute decompensated CHF.

Designer peptide, Hypotension, Renin suppression
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© American Journal of Hypertension, Ltd. 2001
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