Beschreibung:
<jats:sec><jats:title>Background</jats:title><jats:p>The 17‐amino‐acid (AA) ring of C‐type natriuretic peptide (CNP) is essential for activation of NP receptor (NPR)‐B and the 2<jats:sup>nd</jats:sup> messenger cGMP. CNP induces minimal hypotension as NPR‐B is more abundantly found in veins <jats:italic>vs</jats:italic> 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.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>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<jats:sup> †</jats:sup>, BL <jats:italic>vs</jats:italic> 30 min infusion.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>CAB‐NP increased plasma cGMP (3.5±0.6 to 10.9±1<jats:sup> †</jats:sup> 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<jats:sup>+</jats:sup> excretion (19±7 to 191±55* †Eq/min). Proximal (85±3 to 68±1<jats:sup> †</jats:sup> %) and distal (98±1 to 91±2<jats:sup> †</jats:sup> %) 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<jats:sup> †</jats:sup> mmHg) and RAP (3±1 to 2±1* mmHg) were reduced. Plasma renin activity (11±1 to 2±0.3<jats:sup> †</jats:sup> ng/mL/hr) and aldosterone (15±4 to 7±2* ng/dL) were suppressed.</jats:p></jats:sec><jats:sec><jats:title>Conclusions</jats:title><jats:p>CAB‐NP exerts favorable <jats:italic>in vivo</jats:italic> actions without excessively lowering BP. The therapeutic potential of CAB‐NP warrants further studies.</jats:p><jats:p>Supported by the NIH, HFSA, and ASCPT.</jats:p></jats:sec>