Fernandes Elissa Kerli, Türck Patrick, Carraro Cristina Campos, de Mello Palma Victor, de Lima Rosa Gabriel, Coitinho Adriana Simon, Visioli Fernanda, Belló-Klein Adriane, de Castro Alexandre Luz, Araujo Alex Sander da Rosa
Laboratory of Cardiovascular Physiology, Universidade Federal do Rio Grande do Sul-UFRGS, Porto Alegre, RS, Brasil.
Oral Pathology Laboratory of the Faculty of Dentistry, Universidade Federal do Rio Grande do Sul-UFRGS, Porto Alegre, RS, Brasil ; and.
J Cardiovasc Pharmacol. 2025 Feb 1;85(2):166-175. doi: 10.1097/FJC.0000000000001657.
Adrenergic overstimulation is detrimental to the left ventricle. However, its effects on the right ventricle (RV) are not clear. Because adrenergic overload increases metabolic demand and oxidative stress, boldine could be a therapeutic option in the treatment of cardiovascular disease because of its antioxidant role. This study aimed to investigate the impact of adrenergic overload on RV remodeling and the cardioprotective effect of boldine. Animals were divided into 4 groups: control (C), boldine (25 mg/kg i. P .) (B), isoproterenol (ISO) (5 mg/kg subcutaneously), and boldine+isoproterenol (B+ISO). Echocardiography, Fulton index (FI), histology, oxidative stress, inflammation, and β-adrenergic receptor (ADR) were analyzed. The diastolic parasternal length [C 0.698 (0.623-0.724) versus ISO 0.77 (0.73-0.81)], FI [C 0.268 (0.231-0.275) versus ISO 0.340 (0.280-0.353)], inflammatory infiltration (∼40%), and ADR [C 0.78 (0.71-0.84) versus ISO 1.74 (1.52-2.00)] were increased in the ISO group ( P < 0.05). Boldine treatment (B+ISO) reduced the FI [0.240 (0.228-0.263)], lipid peroxidation [2.07 (2.01-2.61)], and ADR [0.71(0.62-0.80)]. Boldine increased total SH levels in B+ISO [C 2.4 (1.78-2.71); ISO 4.01 (2.95-4.66) versus B+ISO 6.77(5.15-8.60)] ( P < 0.05). There was a positive correlation between lipid peroxidation and the FI, and a negative correlation between total SH and the FI ( P < 0.05). This is the first study to explore the effects of adrenergic overstimulation on RV and the protective effect of boldine. Such data pave the way for further research involving RV remodeling, such as in pulmonary hypertension, and a new therapeutic option.
肾上腺素能过度刺激对左心室有害。然而，其对右心室（RV）的影响尚不清楚。由于肾上腺素能过载会增加代谢需求和氧化应激，波耳定碱因其抗氧化作用可能成为治疗心血管疾病的一种选择。本研究旨在探讨肾上腺素能过载对右心室重构的影响以及波耳定碱的心脏保护作用。将动物分为4组：对照组（C）、波耳定碱组（25mg/kg腹腔注射）（B）、异丙肾上腺素组（ISO）（5mg/kg皮下注射）和波耳定碱+异丙肾上腺素组（B+ISO）。分析了超声心动图、富尔顿指数（FI）、组织学、氧化应激、炎症和β-肾上腺素能受体（ADR）。ISO组的舒张期胸骨旁长度[C组0.698（0.623 - 0.724）对比ISO组0.77（0.73 - 0.81）]、FI[C组0.268（0.231 - 0.275）对比ISO组0.340（0.280 - 0.353）]、炎症浸润（约40%）和ADR[C组0.78（0.71 - 0.84）对比ISO组1.74（1.52 - 2.00）]均增加（P<0.05）。波耳定碱治疗（B+ISO）降低了FI[0.240（0.228 - 0.263）]、脂质过氧化[2.07（2.01 - 2.61）]和ADR[0.71（0.62 - 0.80）]。波耳定碱增加了B+ISO组的总SH水平[C组2.4（1.78 - 2.71）；ISO组4.01（2.95 - 4.66）对比B+ISO组6.77（5.15 - 8.60）]（P<0.05）。脂质过氧化与FI呈正相关，总SH与FI呈负相关（P<0.05）。这是第一项探索肾上腺素能过度刺激对右心室的影响以及波耳定碱保护作用的研究。这些数据为进一步研究右心室重构（如肺动脉高压）及新的治疗选择铺平了道路。
