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A novel designer natriuretic peptide integrating human C‐type natriuretic peptide, atrial natriuretic peptide, and B‐type natriuretic peptide
Author(s) -
Lee Candace Y.W.,
Burnett John C.
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.756.9
Subject(s) - natriuretic peptide , atrial natriuretic peptide , medicine , endocrinology , chemistry , aldosterone , peptide , excretion , npr2 , renin–angiotensin system , blood pressure , heart failure , biochemistry
Background The 17‐amino‐acid (AA) ring of C‐type natriuretic peptide (CNP) is essential for activation of NP receptor (NPR)‐B and the 2 nd messenger cGMP. CNP induces minimal hypotension as NPR‐B is more abundantly found in veins vs arteries, but possesses limited renal properties. We designed a novel peptide fusing the CNP ring with AAs from ANP and BNP to test our hypothesis that this unique peptide, CAB‐NP, would exert enhanced renal actions without inducing excessive hypotension. Methods CAB‐NP was synthesized (SLRRSSCFGLKLDRIGSMSGLGCKVLRRH) and infused (21 pmol/kg/min iv) in 5 anesthetized dogs. GFR was assessed by inulin clearance. Mean±SE, P<.05*, <.01 † , BL vs 30 min infusion. Results CAB‐NP increased plasma cGMP (3.5±0.6 to 10.9±1 † pmol/mL), urinary cGMP excretion (980±96 to 4587±825* pmol/min), net renal cGMP generation (823±88 to 4091±824* pmol/min), urine flow (0.2±.03 to 1.2±.4* mL/min) and Na + excretion (19±7 to 191±55* †Eq/min). Proximal (85±3 to 68±1 † %) and distal (98±1 to 91±2 † %) FRNa were reduced; GFR was preserved (46±4 to 45±3 mL/min). MAP mildly decreased (121±4 to 111±5* mmHg). PCWP (6±1 to 4±1 † mmHg) and RAP (3±1 to 2±1* mmHg) were reduced. Plasma renin activity (11±1 to 2±0.3 † ng/mL/hr) and aldosterone (15±4 to 7±2* ng/dL) were suppressed. Conclusions CAB‐NP exerts favorable in vivo actions without excessively lowering BP. The therapeutic potential of CAB‐NP warrants further studies. Supported by the NIH, HFSA, and ASCPT.