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1 Cardiorenal Research Laboratory, Division of Cardiovascular Diseases, Department of Internal Medicine and Physiology, Mayo Clinic College Of Medicine, Rochester, MN, USA
* To whom correspondence should be addressed. E-mail: chen.horng{at}mayo.edu.
BACKGROUND: Recent studies have reported that renal function is an important predictor of survival in overt congestive heart failure (CHF). A hallmark of overt CHF is attenuated 3',5'-cyclic guanosine monophosphate (cGMP) production to endogenous atrial natriuretic peptide (ANP) with renal resistance to ANP. ANP and brain natriuretic peptide (BNP) are of myocardial origin while urodilatin (Uro) is thought to be derived from the kidney. Uro has been isolated from human urine with an amino acid (AA) sequence identical to ANP but with an N-terminal extension of four AA residues. All three peptides are agonists to the natriuretic peptide-A receptor. The objective of the current study was to compare the cardiorenal and humoral actions of ANP, BNP and Uro in experimental overt CHF, thus providing new insights into the biology of the natriuretic peptides in overt CHF METHODS: We determined the cardiorenal and humoral actions of 90 minutes intravenous equimolar infusion of ANP (n=6), BNP (n=5) and Uro (n=6) (2 and 10 pmol/kg/min) in 3 separate groups of anesthetized dogs with rapid ventricular pacing induced overt CHF (240 bpm for 10 days). RESULTS: BNP resulted in increases in urinary sodium excretion (UNaV) (2.2±0.7 to 164±76 µEq/min, p<0.05) and glomerular filtration rate (GFR) (27±4 to 52±11 ml/min, p<0.05) which were greater as compared to Uro (p<0.05 BNP vs Uro), while ANP did not result in increases in either UNaV or GFR. The increases in plasma cGMP (25±2 to 38±2 pmol/ml, p<0.05) and urinary cGMP excretion with BNP (1618±151 to 6124±995 pmol/min, p<0.05) were similar to Uro, however there was no change with ANP. Cardiac filling pressures were reduced in all three groups. CONCLUSION: In this model of experimental overt CHF, ANP, BNP and Uro, agonists of the natriuretic peptide-A receptor, have differential renal properties. These studies also support the conclusion that in experimental overt CHF, renal resistance to natriuretic peptides in increasing rank order is BNP< Uro< ANP.
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