Targeting Cardiac Myocyte Na<sup>+</sup>-K<sup>+</sup> Pump Function With β3 Adrenergic Agonist in Rabbit Model of Severe Congestive Heart Failure.
Fry, NAS
Liu, C-C
Garcia, A
Hamilton, EJ
Karimi Galougahi, K
Kim, YJ
Whalley, DW
Bundgaard, H
Rasmussen, HH
Hamilton, EJ
Karimi Galougahi, K
Kim, YJ
Whalley, DW
Bundgaard, H
Rasmussen, HH
- Publisher:
- Ovid Technologies (Wolters Kluwer Health)
- Publication Type:
- Journal Article
- Citation:
- Circulation. Heart failure, 2020, 13, (9), pp. e006753
- Issue Date:
- 2020-09
Closed Access
| Filename | Description | Size | |||
|---|---|---|---|---|---|
| 17244774_4433684390005671.pdf | Submitted version | 1.72 MB |
Copyright Clearance Process
- Recently Added
- In Progress
- Closed Access
This item is closed access and not available.
Background
Abnormally high cytosolic Na+ concentrations in advanced heart failure impair myocardial contractility. Stimulation of the membrane Na+-K+ pump should lower Na+ concentrations, and the β3 adrenoceptor (β3 AR) mediates pump stimulation in myocytes. We examined if β3 AR-selective agonists given in vivo increase myocyte Na+-K+ pump activity and reverse organ congestion in severe heart failure (HF).Methods
Indices for HF were lung-, heart-, and liver: body weight ratios and ascites after circumflex coronary artery ligation in rabbits. Na+-K+ pump current, Ip, was measured in voltage-clamped myocytes from noninfarct myocardium. Rabbits were treated with the β3 AR agonists CL316,243 or ASP9531, starting 2 weeks after coronary ligation.Results
Coronary ligation caused ascites in most rabbits, significantly increased lung-, heart-, and liver: body weight ratios, and decreased Ip relative to that for 10 sham-operated rabbits. Treatment with CL316,243 for 3 days significantly reduced lung-, heart-, and liver: body weight ratios and prevalence of ascites in 8 rabbits with HF relative to indices for 13 untreated rabbits with HF. It also increased Ip significantly to levels of myocytes from sham-operated rabbits. Treatment with ASP9531 for 14 days significantly reduced indices of organ congestion in 6 rabbits with HF relative to indices of 6 untreated rabbits, and it eliminated ascites. β3 AR agonists did not significantly change heart rates or blood pressures.Conclusions
Parallel β3 AR agonists-induced reversal of Na+-K+ pump inhibition and indices of congestion suggest pump inhibition is a useful target for treatment with β3 AR agonists in congestive HF.Please use this identifier to cite or link to this item: