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Neutral endopeptidase inhibitor suppresses the early phase of atrial electrical remodeling in a canine rapid atrial pacing model.

Imaki R, Niwano S, Niwano H, Satoh D, Yoshida T, Masaki Y, Izumi T - Indian Pacing Electrophysiol J (2008)

Bottom Line: Ten beagle dogs were used and divided into two groups with and without candoxatril, a neutral endopeptidase inhibitor preadministration.Candoxatril: 44.5 +/- 12.28 fmol/mg, p = 0.034) as well as that of plasma cyclic GMP (Control: 32 +/- 5.5 vs.Candoxatril: 42 +/- 7.1 pg/ml, p = 0.028).

View Article: PubMed Central - PubMed

Affiliation: Department of Internal Medicine/Cardiology, Kitasato University School of Medicine, Sagamihara, Japan. imakiii@hotmail.com

ABSTRACT

Introduction: We examined the acute effects of neutral endopeptidase inhibitor on the hemodynamics and electrical properties of dogs subjected to rapid atrial pacing.

Methods: Ten beagle dogs were used and divided into two groups with and without candoxatril, a neutral endopeptidase inhibitor preadministration. Before and after the 6 hours rapid atrial pacing from the right atrial appendage, the hemodynamics, atrial effective refractory period, and monophasic action potential duration of the right atrial appendage were measured and blood samples were collected. Atrial tissue was also excised after the experiment.

Results: Candoxatril significantly increased plasma ANP levels (Control: 88.4 +/- 50.25 vs. Candoxatril: 197.1 +/- 32.09 pg/ml, p = 0.004) and prevented reductions in atrial effective refractory period and monophasic action potential duration. We further demonstrated that the treated animals exhibited significantly higher levels of atrial tissue cyclic GMP (Control: 28.1 +/- 1.60 fmol/mg vs. Candoxatril: 44.5 +/- 12.28 fmol/mg, p = 0.034) as well as that of plasma cyclic GMP (Control: 32 +/- 5.5 vs. Candoxatril: 42 +/- 7.1 pg/ml, p = 0.028).

Conclusion: Candoxatril suppressed the shortening of atrial effective refractory period and monophasic action potential duration in the rapid atrial pacing model. As plasma ANP and the atrial tissue levels of cyclic GMP were higher in the Candoxatril group than the control, this effect was considered to appear through the reduction of calcium overload caused by ANP and cyclic GMP.

No MeSH data available.


Changes in plasma concentrations of (a) ANP, (b) cyclic GMP, (c) renin activity, (d) angiotensin II and (e) aldosterone.  The ANP level was significantly increased by rapid pacing in both groups, and that of after the rapid pacing was higher in the Cx group than the control.  The level of cyclic GMP was not changed significantly by rapid pacing, but the level was higher in the Cx group than the control.  There was no difference between the two groups in renin activity and angiotensin II levels.  The level of aldosterone was increased in the control group but not in the Cx group.  See text for discussion.* p<0.05
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Figure 4: Changes in plasma concentrations of (a) ANP, (b) cyclic GMP, (c) renin activity, (d) angiotensin II and (e) aldosterone. The ANP level was significantly increased by rapid pacing in both groups, and that of after the rapid pacing was higher in the Cx group than the control. The level of cyclic GMP was not changed significantly by rapid pacing, but the level was higher in the Cx group than the control. There was no difference between the two groups in renin activity and angiotensin II levels. The level of aldosterone was increased in the control group but not in the Cx group. See text for discussion.* p<0.05

Mentions: Changes in plasma concentrations of ANP, cyclic GMP, renin activity, Ang II and aldosterone are shown in Figure 4. The plasma level of ANP was significantly increased by rapid pacing in both groups (control: from 25.6 ± 9.05 to 88.4 ± 50.25 pg/ml, p = 0.033, Cx: from 75.8 ± 48.63 to 197.1 ± 32.09 pg/ml, p = 0.014), and that of after rapid pacing was higher in the Cx group than the control (88.4 ± 50.25 vs. 197.1 ± 32.09 pg/ml p = 0.004). There was no difference between the two groups in renin activity and angiotensin II levels. The plasma level of aldosterone was increased in the control group (from 61 ± 63.2 to 256 ± 133.1 pg/ml, p = 0.028), but not in the Cx group after rapid pacing (from 32 ± 26.4 to 40 ± 20.6 pg/ml, p = 0.753).


Neutral endopeptidase inhibitor suppresses the early phase of atrial electrical remodeling in a canine rapid atrial pacing model.

Imaki R, Niwano S, Niwano H, Satoh D, Yoshida T, Masaki Y, Izumi T - Indian Pacing Electrophysiol J (2008)

Changes in plasma concentrations of (a) ANP, (b) cyclic GMP, (c) renin activity, (d) angiotensin II and (e) aldosterone.  The ANP level was significantly increased by rapid pacing in both groups, and that of after the rapid pacing was higher in the Cx group than the control.  The level of cyclic GMP was not changed significantly by rapid pacing, but the level was higher in the Cx group than the control.  There was no difference between the two groups in renin activity and angiotensin II levels.  The level of aldosterone was increased in the control group but not in the Cx group.  See text for discussion.* p<0.05
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2267894&req=5

Figure 4: Changes in plasma concentrations of (a) ANP, (b) cyclic GMP, (c) renin activity, (d) angiotensin II and (e) aldosterone. The ANP level was significantly increased by rapid pacing in both groups, and that of after the rapid pacing was higher in the Cx group than the control. The level of cyclic GMP was not changed significantly by rapid pacing, but the level was higher in the Cx group than the control. There was no difference between the two groups in renin activity and angiotensin II levels. The level of aldosterone was increased in the control group but not in the Cx group. See text for discussion.* p<0.05
Mentions: Changes in plasma concentrations of ANP, cyclic GMP, renin activity, Ang II and aldosterone are shown in Figure 4. The plasma level of ANP was significantly increased by rapid pacing in both groups (control: from 25.6 ± 9.05 to 88.4 ± 50.25 pg/ml, p = 0.033, Cx: from 75.8 ± 48.63 to 197.1 ± 32.09 pg/ml, p = 0.014), and that of after rapid pacing was higher in the Cx group than the control (88.4 ± 50.25 vs. 197.1 ± 32.09 pg/ml p = 0.004). There was no difference between the two groups in renin activity and angiotensin II levels. The plasma level of aldosterone was increased in the control group (from 61 ± 63.2 to 256 ± 133.1 pg/ml, p = 0.028), but not in the Cx group after rapid pacing (from 32 ± 26.4 to 40 ± 20.6 pg/ml, p = 0.753).

Bottom Line: Ten beagle dogs were used and divided into two groups with and without candoxatril, a neutral endopeptidase inhibitor preadministration.Candoxatril: 44.5 +/- 12.28 fmol/mg, p = 0.034) as well as that of plasma cyclic GMP (Control: 32 +/- 5.5 vs.Candoxatril: 42 +/- 7.1 pg/ml, p = 0.028).

View Article: PubMed Central - PubMed

Affiliation: Department of Internal Medicine/Cardiology, Kitasato University School of Medicine, Sagamihara, Japan. imakiii@hotmail.com

ABSTRACT

Introduction: We examined the acute effects of neutral endopeptidase inhibitor on the hemodynamics and electrical properties of dogs subjected to rapid atrial pacing.

Methods: Ten beagle dogs were used and divided into two groups with and without candoxatril, a neutral endopeptidase inhibitor preadministration. Before and after the 6 hours rapid atrial pacing from the right atrial appendage, the hemodynamics, atrial effective refractory period, and monophasic action potential duration of the right atrial appendage were measured and blood samples were collected. Atrial tissue was also excised after the experiment.

Results: Candoxatril significantly increased plasma ANP levels (Control: 88.4 +/- 50.25 vs. Candoxatril: 197.1 +/- 32.09 pg/ml, p = 0.004) and prevented reductions in atrial effective refractory period and monophasic action potential duration. We further demonstrated that the treated animals exhibited significantly higher levels of atrial tissue cyclic GMP (Control: 28.1 +/- 1.60 fmol/mg vs. Candoxatril: 44.5 +/- 12.28 fmol/mg, p = 0.034) as well as that of plasma cyclic GMP (Control: 32 +/- 5.5 vs. Candoxatril: 42 +/- 7.1 pg/ml, p = 0.028).

Conclusion: Candoxatril suppressed the shortening of atrial effective refractory period and monophasic action potential duration in the rapid atrial pacing model. As plasma ANP and the atrial tissue levels of cyclic GMP were higher in the Candoxatril group than the control, this effect was considered to appear through the reduction of calcium overload caused by ANP and cyclic GMP.

No MeSH data available.