title: Cardiovascular and renal effect of CNAAC: An innovatively designed natriuretic peptide.
abstract: Natriuretic peptides (NPs) have natriuretic, diuretic and vasodilator effects. An innovative natriuretic peptide analogue called CNAAC (a new chimera peptide combining the C-terminus and ring of ANP with the N-terminus of CNP) was designed to determine whether it has any cardiovascular and renal effect. Abdominal aorta of rats were isolated and vascular ring perfusion was employed to compare the vasodilator effect and cGMP excretion effect of CNAAC with natural NPs. Urine volume and urine cGMP levels after intravenous injection of CNAAC and natural NPs were determined. Hemodynamic methods were employed to assess the effect of CNAAC and natural NPs on MAP. CNAAC relaxed abdominal aorta in a dose-dependent manner and was independent of endothelium. The vasodilating effect of CNAAC was significantly attenuated in the presence of NPR-A antibody, GC inhibitor, and KATP inhibitor and was abolished by PKG inhibitor. Abdominal aortic cGMP production increased after incubation with NPs. Urine volume, plasma cGMP, and urine cGMP increased and MAP decreased dramatically after intravenous injection of CNAAC. CNAAC has a potent vasodilating effect, probably by activating K(+) channels via NPR-A/sGC/cGMP pathway. Exogenous administration of CNAAC elicits diuretic and hypotensive effects.
authors.affiliation: Department of Physiology, National Key Discipline of Cell Biology, Fourth Military Medical University, No.169 West Changle Road, Xi'an, 710032 Shaanxi Province, People's Republic of China.
authors.forename: Shumiao
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Department of Physiology, National Key Discipline of Cell Biology, Fourth Military Medical University, No.169 West Changle Road, Xi'an, 710032 Shaanxi Province, People's Republic of China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Geng
authors.affiliation: Department of Neurosurgery, Xijing Hospital, Fourth Military Medical University, No. 17 West Changle Road, Xi'an, 710033 Shaanxi Province, People's Republic of China.
authors.forename: Lei
authors.initials: L
authors.lastname: Zhao
authors.affiliation: Department of Physiology, National Key Discipline of Cell Biology, Fourth Military Medical University, No.169 West Changle Road, Xi'an, 710032 Shaanxi Province, People's Republic of China.
authors.forename: Juan
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Physiology, National Key Discipline of Cell Biology, Fourth Military Medical University, No.169 West Changle Road, Xi'an, 710032 Shaanxi Province, People's Republic of China.
authors.forename: Fei
authors.initials: F
authors.lastname: Tian
authors.affiliation: Department of Physiology, National Key Discipline of Cell Biology, Fourth Military Medical University, No.169 West Changle Road, Xi'an, 710032 Shaanxi Province, People's Republic of China.
authors.forename: Yuemin
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Physiology, National Key Discipline of Cell Biology, Fourth Military Medical University, No.169 West Changle Road, Xi'an, 710032 Shaanxi Province, People's Republic of China.
authors.forename: Rong
authors.initials: R
authors.lastname: Fan
authors.affiliation: Department of Physiology, National Key Discipline of Cell Biology, Fourth Military Medical University, No.169 West Changle Road, Xi'an, 710032 Shaanxi Province, People's Republic of China.
authors.forename: Na
authors.initials: N
authors.lastname: Feng
authors.affiliation: Department of Cardiovascular Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an, 710033 Shaanxi Province, China.
authors.forename: Jincheng
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Cardiovascular Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an, 710033 Shaanxi Province, China. Electronic address: chengl@fmmu.edu.cn.
authors.forename: Liang
authors.initials: L
authors.lastname: Cheng
authors.affiliation: Department of Physiology, National Key Discipline of Cell Biology, Fourth Military Medical University, No.169 West Changle Road, Xi'an, 710032 Shaanxi Province, People's Republic of China. Electronic address: jmpei8@fmmu.edu.cn.
authors.forename: Jianming
authors.initials: J
authors.lastname: Pei
mesh_terms: D000818:Animals; D001012:Aorta, Abdominal / Q000187:drug effects* / Q000378:metabolism; D009320:Atrial Natriuretic Factor / Q000008:administration & dosage / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D006152:Cyclic GMP / Q000378:metabolism; D017869:Cyclic GMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D004231:Diuresis / Q000187:drug effects*; D004232:Diuretics / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D006162:Guanylate Cyclase / Q000037:antagonists & inhibitors / Q000378:metabolism; D066298:In Vitro Techniques; D007275:Injections, Intravenous; D054086:KATP Channels / Q000187:drug effects / Q000378:metabolism; D008297:Male; D020098:Natriuretic Peptide, C-Type / Q000008:administration & dosage / Q000494:pharmacology*; D010455:Peptides / Q000008:administration & dosage / Q000494:pharmacology*; D026902:Potassium Channel Blockers / Q000494:pharmacology; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D017207:Rats, Sprague-Dawley; D017461:Receptors, Atrial Natriuretic Factor / Q000187:drug effects / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage / Q000494:pharmacology*; D015290:Second Messenger Systems / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: C000607546:C(N)AA(C) peptide; D004232:Diuretics; D054086:KATP Channels; D010455:Peptides; D026902:Potassium Channel Blockers; D047428:Protein Kinase Inhibitors; D011993:Recombinant Fusion Proteins; D014665:Vasodilator Agents; D020098:Natriuretic Peptide, C-Type; D009320:Atrial Natriuretic Factor; D017869:Cyclic GMP-Dependent Protein Kinases; D006162:Guanylate Cyclase; D017461:Receptors, Atrial Natriuretic Factor; C091715:atrial natriuretic factor receptor A; D006152:Cyclic GMP
keywords: Cardiovascular effect; Diuresis; Natriuretic peptide; Vasodilation