Cardiovascular and renal actions of C-type natriuretic peptide

Stingo, A. J.; Clavell, Alfredo L.; Aarhus, Lawrence L.; Burnett, John C.

doi:10.1152/ajpheart.1992.262.1.h308

Cited by 77 publications

(62 citation statements)

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“…In addition, we observed no effect on blood pressure in these anesthetized rats either after CNP or after a combined infusion of CNP with (S)-thiorphan. Our findings do not agree with the results of Stingo et al (46), who reported for CNP an significant decrease in blood pressure associated with a significant fall in renal sodium excretion in mongrel dogs.…”

Section: Discussioncontrasting

confidence: 99%

“…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%

“…It has also been found that CNP has a much stronger effect than ANP in lowering blood pressure in anesthetized dogs, whereas ANP is more potent in increasing plasma cGMP and the urinary excretion of sodium and cGMP (46). The reason why CNP did not decrease the blood pressure in hypertensive or normotensive anesthetized rats in this study is so far unclear, but a possible explanation could be the absence of ANP-B receptors in rat kidney (39,40) as mentioned above.…”

Section: Discussionmentioning

confidence: 46%

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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: Discussioncontrasting

confidence: 99%

Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 46%

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

1996

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“…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). Despite conflicting data on acute renal effects of CNP, fluid homeostasis in chronic down-regulation on NPR-B signaling appears to be balanced.…”

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.

114

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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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“…The actions of CNP are different from those described for ANP and BNP. CNP does not show any diuretic or natriuretic actions in dogs and humans while it induces potent hemodynamic effects (31). Also, in contrast to ANP, CNP stimulates prolactin secretion with a hypothalamic site of action (32) and stimulates rather than inhibits water drinking in rats (33).…”

Section: Natriuretic Peptide Familymentioning

confidence: 99%

Oxytocin is a cardiovascular hormone

Gutkowska

Jankowski

Mukaddam‐Daher

et al. 2000

Braz J Med Biol Res

155

108

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Oxytocin (OT), a nonapeptide, was the first hormone to have its biological activities established and chemical structure determined. It was believed that OT is released from hypothalamic nerve terminals of the posterior hypophysis into the circulation where it stimulates uterine contractions during parturition, and milk ejection during lactation. However, equivalent concentrations of OT were found in the male hypophysis, and similar stimuli of OT release were determined for both sexes, suggesting other physiological functions. Indeed, recent studies indicate that OT is involved in cognition, tolerance, adaptation and complex sexual and maternal behaviour, as well as in the regulation of cardiovascular functions. It has long been known that OT induces natriuresis and causes a fall in mean arterial pressure, both after acute and chronic treatment, but the mechanism was not clear. The discovery of the natriuretic family shed new light on this matter. Atrial natriuretic peptide (ANP), a potent natriuretic and vasorelaxant hormone, originally isolated from rat atria, has been found at other sites, including the brain. Blood volume expansion causes ANP release that is believed to be important in the induction of natriuresis and diuresis, which in turn act to reduce the increase in blood volume. Neurohypophysectomy totally abolishes the ANP response to volume expansion. This indicates that one of the major hypophyseal peptides is responsible for ANP release. The role of ANP in OT-induced natriuresis was evaluated, and we hypothesized that the cardio-renal effects of OT are mediated by the release of ANP from the heart. To support this hypothesis, we have demonstrated the presence and synthesis of OT receptors in all heart compartments and the vasculature. The functionality of these receptors has been established by the ability of OT to induce ANP release from perfused heart or atrial slices. Furthermore, we have shown that the heart and large vessels like the aorta and vena cava are sites of OT synthesis. Therefore, locally produced OT may have important regulatory functions within the heart and vascular beds. Such functions may include slowing down of the heart or the regulation of local vascular tone. Correspondence

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Cardiovascular and renal actions of C-type natriuretic peptide

Cited by 77 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

Oxytocin is a cardiovascular hormone

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