Abstract 1412: A Novel Designer Natriuretic and Diuretic Peptide Based Upon an Alternatively Spliced BNP Without Vascular Vasodilatory Actions
BACKGROUND: B-type natriuretic peptide (BNP) is a cardiac peptide with vasodilatory, natriuretic and diuretic properties. Recent studies have suggested that its vasodilatory hypotensive properties may limit the renal actions of BNP, especially in patients with borderline low blood pressure. We have recently identified an alternatively spliced transcript for BNP (ASBNP) that includes a unique and distinct longer carboxyl-terminus consisting of 34 amino acids. Based upon preliminary studies, we generated a truncated form (ASBNP2.1) that contains the first 16 amino acids of the C-terminal of ASBNP.
METHODS: We determined the cardiorenal and humoral actions of intravenous infusion of ASBNP2.1 at 2 pmol/Kg/min, 10 pmol/Kg/min and 100 pmol/Kg /min in 6 normal anesthetized dogs. * p<0.05
RESULTS: IV infusion of ASBNP 2.1 increased natriuresis (from 68±24 to 110±20, 110±14 and 154±10 μEq/min*) and diuresis (from 0.6±0.1 to 1.4±0.3, 1.9±0.5 and 2.3±0.7 ml/min*) which was associated with a decrease in distal tubular sodium reabsorption (from 97±1 to 95±0.6, 95±0.8 and 92±2 %*). Importantly, ASBNP 2.1 did not have any systemic vasodilatory action resulting in no change in mean arterial blood pressure and cardiac-filling pressures even at the highest dose. Renal blood flow and glomerular filtration rate were preserved and there was a strong trend for the suppression of renin despite the marked natriuresis and diuresis. These renal enhancing properties were associated with increases in both plasma cGMP* and urinary cGMP excretion*.
CONCLUSION: We report for the first time that this novel peptide based upon ASBNP has potent diuretic and natriuretic actions without the vasodilatory hypotensive properties. The lack of vasodilatation but with renal actions also suggest that the C-terminus plays a key role in the vascular actions of this peptide offering new insights into vascular-renal structure function of BNP and related peptides. This renal specific peptide may be useful in states of sodium and water overload to enhance renal sodium and water excretion without the detrimental side effect of hypotension.