C-type natriuretic peptide: a selective cardiovascular peptide

Clavell, Alfredo L.; Stingo, A. J.; Wei, Chiming; Heublein, Denise M.; Burnett, John C.

doi:10.1152/ajpregu.1993.264.2.r290

Cited by 84 publications

(73 citation statements)

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“…In agreement with our findings, early studies of the biological activity of CNP in rats showed it to be natriuretic, diuretic, and a vasodepressor when injected intravenously, but the potency of CNP was about 1 % of the related hormones ANP and BNP (38). CNP, given to anesthetized dogs had greater hemodynamic activity than ANP, but it was not natriuretic even when administered directly into the renal artery (46,48) . The observation of no change in sodium excretion is unique to this peptide when compared with ANP or BNP, which in previous studies produced marked natriuresis despite similar systemic hemodynamic changes (49).…”

Section: Discussionsupporting

confidence: 91%

Neutral Endopeptidase Inhibition Potentiates the Effects of Natriuretic Peptides in Renin Transgenic Rats.

1996

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The influence of neutral endopeptidase (NEP) inhibition with (S)-thiorphan on the hormonal, renal, and blood-pressure-lowering effects of an infusion of atrial (ANP), brain (BNP), and C-type natriuretic peptide (CNP) was evaluated in hypertensive transgenic rats (TGR) harboring an additional mouse renin gene (TGR(m(Ren2)27)).These TGR possess an activated natriuretic peptide system as compared with Sprague-Dawley rats (SDR), used in this study as control. (S)-Thiorphan significantly decreased blood pressure in anesthetized TGR but not in anesthetized SDR during the 60-min infusion period. Exogenously administered ANP decreased blood pressure in SDR with no significant effects in TGR after 60 min. In contrast, BNP infusion significantly decreased blood pressure in TGR, while changes in SDR were not significant. The blood pressure was further decreased after combined infusion of ANP and BNP with (S)-thiorphan in TGR. No effect on blood pressure was registered during infusion of CNP in either experimental group. The plasma levels of ANP, BNP, and cGMP were higher in TGR than in SDR, whereas plasma renin activity was lower. Co-administration of ANP, BNP, or CNP with the NEP inhibitor (S)-thiorphan potentiated the plasma ANP, BNP, and cGMP. Infusion of ANP alone did not affect BNP plasma levels of TGR and vice versa. In contrast, CNP infusion increased ANP plasma levels in both TGR and SDR. Renal excretion of sodium and cGMP increased after infusion of (S)-thiorphan and ANP or BNP in both TGR and SDR. The combination of ANP and (S)-thiorphan had a slightly greater effect on urinary excretion of sodium and cGMP in TGR than either compound alone, but the effects were more pronounced in SDR than in TGR. Finally, infusion of CNP alone and in combination with (S)-thiorphan influenced the excretion of sodium and cyclic GMP only slightly. These results indicate that inhibition of neutral endopeptidase by (S)-thiorphan potentiates the hemodynamic and renal effects of natriuretic peptides ANP and BNP, and to some extent those of CNP, in hypertensive TGR and normotensive SDR. In contrast to ANP and BNP, infusion of CNP had no effect on the blood pressure in anesthetized TGR or SDR. Inhibition of NEP therefore seems to be a promising way to potentiate endogenous levels of natriuretic peptides, which may be of therapeutic benefit in cardiovascular diseases such as hypertension or heart failure. (Hypertens Res 1996;19: 229-238) Key Words: neutral endopeptidase 24.11, (S)-thiorphan, ecadotril, TGR(m(Ren2)27), ANP, BNP, CNPThe natriuretic peptides are a family of related polypeptide hormones including atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and C-type natriuretic peptide (CNP). These natriuretic peptides have a common structural motif consisting of a loop of 17 amino acids formed by intramolecular disulfide bonds. Only 6 of the 17 amino acids in this ring differ among the three peptides isolated from the pig, whereas the N-and C-terminals vary both in amino acid composition and length (1,2). Neutral m...

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Section: Discussionsupporting

confidence: 91%

Neutral Endopeptidase Inhibition Potentiates the Effects of Natriuretic Peptides in Renin Transgenic Rats.

1996

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“…This finding is in accordance with previously published data showing that CNP does not influence renal function in humans and dogs after i.v. administration at low dosages (33,34). It has been demonstrated that systemic infusion or bolus administration of supraphysiological CNP concentrations in dogs increased aldosterone release and distal nephron sodium reabsorption, suggesting that CNP regulates tubular reabsorption and not glomerular filtration rate (35).…”

Section: Discussionmentioning

confidence: 99%

Cardiac hypertrophy in transgenic rats expressing a dominant-negative mutant of the natriuretic peptide receptor B

Langenickel

Buttgereit

Pagel-Langenickel

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

115

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Natriuretic peptides (NP) mediate their effects by activating membrane-bound guanylyl cyclase-coupled receptors A (NPR-A) or B (NPR-B). Whereas the pathophysiological role of NPR-A has been widely studied, only limited knowledge on the cardiovascular function of NPR-B is available. In vitro studies suggest antiproliferative and antihypertrophic actions of the NPR-B ligand C-type NP (CNP). Because of the lack of a specific pharmacological inhibitor, these effects could not clearly be attributed to impaired NPR-B signaling. Recently, gene deletion revealed a predominant role of NPR-B in endochondral ossification and development of female reproductive organs. However, morphological abnormalities and premature death of NPR-B-deficient mice preclude detailed cardiovascular phenotyping. In the present study, a dominant-negative mutant (NPR-B⌬KC) was used to characterize CNP-dependent NPR-B signaling in vitro and in transgenic rats. Here we demonstrate that reduced CNP-but not atrial NP-dependent cGMP response attenuates antihypertrophic potency of CNP in vitro. In transgenic rats, NPR-B⌬KC expression selectively reduced NPR-B but not NPR-A signaling. NPR-B⌬KC transgenic rats display progressive, blood pressure-independent cardiac hypertrophy and elevated heart rate. The hypertrophic phenotype is further enhanced in chronic volume overload-induced congestive heart failure. Thus, this study provides evidence linking NPR-B signaling to the control of cardiac growth.C-type natriuretic peptide ͉ knockdown

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“…Of the three NPs, CNP has been shown to be most potent at inhibiting growth‐factor–induced smooth muscle cell migration 81. CNP has only minimal renal actions, but it has been shown to induce vasorelaxation and, interestingly, CNP infusion to dogs has been shown to lower blood pressure more effectively than ANP without natriuretic effect 82. Plasma levels of CNP1‐53 are also elevated in patients with acute decompensated HF,83 and recent data suggest that in addition to CNP1‐22, the CNP1‐53 peptide also has biological actions in in vitro and in vivo models 84.…”

Section: Cnp In the Diseased Heartmentioning

confidence: 99%

Natriuretic Peptides in the Regulation of Cardiovascular Physiology and Metabolic Events

Kerkelä

Ulvila

Magga

2015

JAHA

127

108

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C-type natriuretic peptide: a selective cardiovascular peptide

Cited by 84 publications

References 0 publications

Neutral Endopeptidase Inhibition Potentiates the Effects of Natriuretic Peptides in Renin Transgenic Rats.

Neutral Endopeptidase Inhibition Potentiates the Effects of Natriuretic Peptides in Renin Transgenic Rats.

Cardiac hypertrophy in transgenic rats expressing a dominant-negative mutant of the natriuretic peptide receptor B

Natriuretic Peptides in the Regulation of Cardiovascular Physiology and Metabolic Events

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