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β3 adrenergic agonism: A novel pathway which improves right ventricular‐pulmonary arterial hemodynamics in pulmonary arterial hypertension
- Source :
- Physiological Reports, Vol 11, Iss 1, Pp n/a-n/a (2023)
- Publication Year :
- 2023
- Publisher :
- Wiley, 2023.
-
Abstract
- Abstract Efficacy of therapies that target the downstream nitric oxide (NO) pathway in pulmonary arterial hypertension (PAH) depends on the bioavailability of NO. Reduced NO level in PAH is secondary to “uncoupling” of endothelial nitric oxide synthase (eNOS). Stimulation of β3 adrenergic receptors (β3 ARs) may lead to the recoupling of NOS and therefore be beneficial in PAH. We aimed to examine the efficacy of β3 AR agonism as a novel pathway in experimental PAH. In hypoxia (5 weeks) and Sugen hypoxia (hypoxia for 5 weeks + SU5416 injection) models of PAH, we examined the effects of the selective β3 AR agonist CL316243. We measured echocardiographic indices and invasive right ventricular (RV)–pulmonary arterial (PA) hemodynamics and compared CL316243 with riociguat and sildenafil. We assessed treatment effects on RV–PA remodeling, oxidative stress, and eNOS glutathionylation, an oxidative modification that uncouples eNOS. Compared with normoxic mice, RV systolic pressure was increased in the control hypoxic mice (p
Details
- Language :
- English
- ISSN :
- 2051817X
- Volume :
- 11
- Issue :
- 1
- Database :
- Directory of Open Access Journals
- Journal :
- Physiological Reports
- Publication Type :
- Academic Journal
- Accession number :
- edsdoj.34047c3e9bc0488cbfa7b2dea5a1826e
- Document Type :
- article
- Full Text :
- https://doi.org/10.14814/phy2.15549