Limits...
AC-NP: a novel chimeric peptide with natriuretic and vasorelaxing actions.

Chen BY, Chen JK, Zhu MZ, Zhang DL, Sun JS, Pei JM, Feng HS, Zhu XX, Jin J, Yu J - PLoS ONE (2011)

Bottom Line: In relaxation of isolated abdominal aorta from rat, AC-NP was equally effective to ANP, CNP and VNP.Elevated levels of 3',5'-guanosine monophosphate (cGMP) in plasma and urine cGMP excretion indicated the participation of cGMP in the functions of AC-NP.Taken together, innovative designed AD-NP might be a new candidate therapeutic peptide against cardiorenal disorders.

View Article: PubMed Central - PubMed

Affiliation: Department of Radiology, Tangdu Hospital, Fourth Military Medical University, Xi'an, China.

ABSTRACT
The aim of this study was to evaluate the cardiovascular and renal activities of a newly designed natriuretic peptide (NP). Here, we engineered a novel 28-amino acid chimeric peptide, termed AC-NP that combined the 17-amino acid ring of C type natriuretic peptide (CNP) with the 6-amino acid N-terminus and 5-amino acid C-terminus of atrial natriuretic peptide (ANP). Both in vitro and in vivo experiments were performed to determine the actions of AC-NP. In normal rats, AC-NP proved to be more potentially diuretic, natriuretic and hypotensive compared with other NPs, such as ANP, CNP and vasonatrin peptide (VNP), which is another man-made NP. In relaxation of isolated abdominal aorta from rat, AC-NP was equally effective to ANP, CNP and VNP. Elevated levels of 3',5'-guanosine monophosphate (cGMP) in plasma and urine cGMP excretion indicated the participation of cGMP in the functions of AC-NP. Taken together, innovative designed AD-NP might be a new candidate therapeutic peptide against cardiorenal disorders.

Show MeSH

Related in: MedlinePlus

Relaxant responses of isolated abdominal aorta from rat to ANP, CNP, VNP or AC-NP.Endothelium-intact rings cut from abdominal aorta of 5 rats (n = 5) were suspended in organ chambers. In one-half of the rings, the endothelium was removed by gently rubbing the intimal surface with a cotton swab. After setting resting force to about 500 mg weight, artery rings were contracted with 10−6 M extracellular norepinephrine (NE) and relaxed with ANP, CNP, VNP or AC-NP. (A) The representative curves of relaxation to cumulatively increasing concentration of AC-NP. (B) Dose dependent response of isolated rat abdominal aorta with or without endothelium to cumulatively increasing concentration of AC-NP. (C) Maximal responses to ANP, CNP, VNP and AC-NP at the dose of 10−6 M, or saline as control. The maximal contraction induced by 10−6 M extracellular NE was arbitrarily set as 100%. Data of relaxation are the reduced (minus) percentages of maximal contractile amplitudes to 10−6 M NE, and presented as mean ± SEM. Symbols obscure some of the smaller error bars.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC3101257&req=5

pone-0020477-g002: Relaxant responses of isolated abdominal aorta from rat to ANP, CNP, VNP or AC-NP.Endothelium-intact rings cut from abdominal aorta of 5 rats (n = 5) were suspended in organ chambers. In one-half of the rings, the endothelium was removed by gently rubbing the intimal surface with a cotton swab. After setting resting force to about 500 mg weight, artery rings were contracted with 10−6 M extracellular norepinephrine (NE) and relaxed with ANP, CNP, VNP or AC-NP. (A) The representative curves of relaxation to cumulatively increasing concentration of AC-NP. (B) Dose dependent response of isolated rat abdominal aorta with or without endothelium to cumulatively increasing concentration of AC-NP. (C) Maximal responses to ANP, CNP, VNP and AC-NP at the dose of 10−6 M, or saline as control. The maximal contraction induced by 10−6 M extracellular NE was arbitrarily set as 100%. Data of relaxation are the reduced (minus) percentages of maximal contractile amplitudes to 10−6 M NE, and presented as mean ± SEM. Symbols obscure some of the smaller error bars.

Mentions: In the representative concentration-response curves illustrated in Figure 2A, AC-NP reduced the contractile responses of the arterial ring to 10−6 M NE in a dose dependent manner. The equivalent responses of deendothelium and endothelium-intact artery rings to AC-NP indicated that vasodilating actions of AC-NP are independent of endothelium (Fig. 2B). The maximal relaxations induced by ANP, CNP, VNP or AC-NP in isolated rat abdominal aorta were shown in Figure 2C. ANP, CNP, VNP or AC-NP at the dose of 10−6 M all caused significant relaxations compared with saline control (P<0.05, n = 5). The potency for relaxation in isolated rat abdominal aorta for the peptides was shown as: CNP > AC-NP > VNP > ANP, but not statistically significant.


AC-NP: a novel chimeric peptide with natriuretic and vasorelaxing actions.

Chen BY, Chen JK, Zhu MZ, Zhang DL, Sun JS, Pei JM, Feng HS, Zhu XX, Jin J, Yu J - PLoS ONE (2011)

Relaxant responses of isolated abdominal aorta from rat to ANP, CNP, VNP or AC-NP.Endothelium-intact rings cut from abdominal aorta of 5 rats (n = 5) were suspended in organ chambers. In one-half of the rings, the endothelium was removed by gently rubbing the intimal surface with a cotton swab. After setting resting force to about 500 mg weight, artery rings were contracted with 10−6 M extracellular norepinephrine (NE) and relaxed with ANP, CNP, VNP or AC-NP. (A) The representative curves of relaxation to cumulatively increasing concentration of AC-NP. (B) Dose dependent response of isolated rat abdominal aorta with or without endothelium to cumulatively increasing concentration of AC-NP. (C) Maximal responses to ANP, CNP, VNP and AC-NP at the dose of 10−6 M, or saline as control. The maximal contraction induced by 10−6 M extracellular NE was arbitrarily set as 100%. Data of relaxation are the reduced (minus) percentages of maximal contractile amplitudes to 10−6 M NE, and presented as mean ± SEM. Symbols obscure some of the smaller error bars.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3101257&req=5

pone-0020477-g002: Relaxant responses of isolated abdominal aorta from rat to ANP, CNP, VNP or AC-NP.Endothelium-intact rings cut from abdominal aorta of 5 rats (n = 5) were suspended in organ chambers. In one-half of the rings, the endothelium was removed by gently rubbing the intimal surface with a cotton swab. After setting resting force to about 500 mg weight, artery rings were contracted with 10−6 M extracellular norepinephrine (NE) and relaxed with ANP, CNP, VNP or AC-NP. (A) The representative curves of relaxation to cumulatively increasing concentration of AC-NP. (B) Dose dependent response of isolated rat abdominal aorta with or without endothelium to cumulatively increasing concentration of AC-NP. (C) Maximal responses to ANP, CNP, VNP and AC-NP at the dose of 10−6 M, or saline as control. The maximal contraction induced by 10−6 M extracellular NE was arbitrarily set as 100%. Data of relaxation are the reduced (minus) percentages of maximal contractile amplitudes to 10−6 M NE, and presented as mean ± SEM. Symbols obscure some of the smaller error bars.
Mentions: In the representative concentration-response curves illustrated in Figure 2A, AC-NP reduced the contractile responses of the arterial ring to 10−6 M NE in a dose dependent manner. The equivalent responses of deendothelium and endothelium-intact artery rings to AC-NP indicated that vasodilating actions of AC-NP are independent of endothelium (Fig. 2B). The maximal relaxations induced by ANP, CNP, VNP or AC-NP in isolated rat abdominal aorta were shown in Figure 2C. ANP, CNP, VNP or AC-NP at the dose of 10−6 M all caused significant relaxations compared with saline control (P<0.05, n = 5). The potency for relaxation in isolated rat abdominal aorta for the peptides was shown as: CNP > AC-NP > VNP > ANP, but not statistically significant.

Bottom Line: In relaxation of isolated abdominal aorta from rat, AC-NP was equally effective to ANP, CNP and VNP.Elevated levels of 3',5'-guanosine monophosphate (cGMP) in plasma and urine cGMP excretion indicated the participation of cGMP in the functions of AC-NP.Taken together, innovative designed AD-NP might be a new candidate therapeutic peptide against cardiorenal disorders.

View Article: PubMed Central - PubMed

Affiliation: Department of Radiology, Tangdu Hospital, Fourth Military Medical University, Xi'an, China.

ABSTRACT
The aim of this study was to evaluate the cardiovascular and renal activities of a newly designed natriuretic peptide (NP). Here, we engineered a novel 28-amino acid chimeric peptide, termed AC-NP that combined the 17-amino acid ring of C type natriuretic peptide (CNP) with the 6-amino acid N-terminus and 5-amino acid C-terminus of atrial natriuretic peptide (ANP). Both in vitro and in vivo experiments were performed to determine the actions of AC-NP. In normal rats, AC-NP proved to be more potentially diuretic, natriuretic and hypotensive compared with other NPs, such as ANP, CNP and vasonatrin peptide (VNP), which is another man-made NP. In relaxation of isolated abdominal aorta from rat, AC-NP was equally effective to ANP, CNP and VNP. Elevated levels of 3',5'-guanosine monophosphate (cGMP) in plasma and urine cGMP excretion indicated the participation of cGMP in the functions of AC-NP. Taken together, innovative designed AD-NP might be a new candidate therapeutic peptide against cardiorenal disorders.

Show MeSH
Related in: MedlinePlus