Design, Synthesis, and Actions of a Novel Chimeric Natriuretic Peptide: CD-NP
Ondrej Lisy, MD, PhD*,*,
Brenda K. Huntley*,
Daniel J. McCormick, PhD ,
Paul A. Kurlansky, MD and
John C. Burnett, Jr, MD*
* Cardiorenal Research Laboratory, Division of Cardiovascular Diseases, Mayo Clinic and Mayo Clinic College of Medicine, Rochester, Minnesota
Laboratory of Expression Proteomics and Protein Chemistry, Mayo Clinic and Mayo Clinic College of Medicine, Rochester, Minnesota
Miami Heart Research Institute, Miami, Florida.
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Figure 1 AA Sequence and Structure of a CNP and Novel Chimeric Natriuretic Peptide C-Terminus of DNP and CD-NP
C-type natriuretic peptide (CNP) is a 22-amino acid (AA) endothelial-cell-derived natriuretic peptide, C-terminus of Dendroaspis natriuretic peptide (DNP) is a 15-AA chimeric natriuretic peptide, and CD-NP is a 37-AA-designed chimeric natriuretic peptide.
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Figure 2 Effect of C-Terminus of DNP on UNaV and UV in Normal Dogs
Data are expressed as means ± SE. C-terminus, intravenous infusion of 42 ng/kg/min of C-terminus, n = 6. *p < 0.05 versus baseline. DNP = Dendroaspis natriuretic peptide; UNaV = urinary excretion of sodium; UV = urine flow.
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Figure 3 Effect of CD-NP on MAP, RAP, and PCWP in Normal Dogs
Data are expressed as means ± SE. n = 6. *p < 0.05 versus baseline. CD-NP 10 = dose of CD-NP 10 ng/kg/min; CD-NP 50 = dose of CD-NP 50 ng/kg/min; CD-NP 100 = dose of CD-NP 100 ng/kg/min; MAP = mean arterial pressure; PCWP = pulmonary capillary pressure; RAP = right atrial pressure.
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Figure 4 Effect of CD-NP on UNaV, UV, and GFR in Normal Dogs
Data are expressed as means ± SE. n = 6. *p < 0.05 versus baseline. GFR = glomerular filtration rate; other abbreviations as in Figures 2 and 3.
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Figure 5 Effect of CD-NP on Proximal and Distal Fractional Sodium Reabsorption in Normal Dogs
Data are expressed as means ± SE. n = 6. *p < 0.05 versus baseline. DFRNa = distal fractional sodium reabsorption; PFRNa = proximal fractional sodium reabsorption; other abbreviations as in Figure 3.
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Figure 6 Effect of CD-NP and Equimolar Doses of Human BNP in 2 Groups of Normal Dogs
Data are expressed as means ± SE. n = 6 in each group. *p < 0.05 versus baseline; p < 0.05 between groups. Solid bars = CD-NP; open bars = B-type natriuretic peptide (BNP). Abbreviations as in Figures 3 and 4.
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Figure 7 Effect of CD-NP on cGMP Generation and Antiproliferative Actions of CD-NP in Human CFs
(A) Cyclic 3'5' guanosine monophosphate (cGMP) generation in human cardiac fibroblasts (CFs). Data are expressed as means ± SE. *p < 0.05 versus no treatment; **p < 0.05 versus CP-NP 10–11M; +p < 0.05 versus CD-NP 10–8 M. (B) Antiproliferative actions of CD-NP in human CFs. Bar graph reports colormetric bromodeoxyuridine (BrdU) uptake in optical density units as measured by colorimetry. Data are expressed as means ± standard error. *p < 0.05 versus control. Cardiotrophin-1 = proliferation of fibroblasts by cardiotrophin-1; Cardiotrophin-1 + CD-NP = CD-NP added to cardiotrophin-1 stimulated fibroblasts; Control = untreated human cardiac fibroblasts.
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