Emetine treatment reduces blood pressure in spontaneously hypertensive rats

Vascular remodeling is a significant contributor to hypertension, a chronic disease that is the overall leading cause of death in the US. About half of US adults are hypertensive and many of these patients present with resistant hypertension, which is defined as an inability to achieve desired blood pressure levels despite the use of three or more antihypertensive medications. Thus, discovering new avenues of treatment or therapeutic targets is imperative. Emetine is an emetic compound that has been shown to slow cancer cell proliferation, increase apoptosis, induce oxidative stress and slow protein synthesis. While its ability to bind ribosomes contributes to its ability to alter protein synthesis, a novel study discovered that emetine causes release of acidic intracellular and Golgi Ca 2+ stores. Disruption of lumenal Golgi Ca 2+ homeostasis could have wide ranging effects on key Golgi functions. Previous data indicated that reduced Golgi Ca 2+ stores in vascular smooth muscle cells (VSMCs) affected contractility and slowed pathological remodeling during the development of hypertension. Based on these findings, we hypothesize that chronic delivery of emetine will lower high blood pressure through disruption of Golgi Ca 2+ stores and protein synthesis, which will improve vascular remodeling by reducing proliferation. Utilizing surgically implanted telemeters to measure chronic blood pressure, we observed that male spontaneously hypertensive rats (SHRs) treated with emetine (0.05 mg/kg bodyweight/day) for 21 days had significantly attenuated endpoint blood pressure compared to vehicle treated rats (156 ± 2 vs 146 ± 1 mmHg, p=0.02). There were no differences in endpoint body, heart, or kidney weights. Ongoing studies will use RNAseq, Western blots, and immunohistochemistry to assess changes to vascular proliferation/apoptosis, and identify additional novel pathways affected by emetine treatment. Myography experiments of control and emetine-treated resistance vessels will shed additional light on acute effects and contractile changes following prolonged treatment. Our data indicate that emetine may have a beneficial effect on systemic hypertension, but further work is required to reveal the mechanism of action. We anticipate that our findings will determine that Golgi Ca 2+ homeostasis may be a promising and previously unknown mechanism to target in treating hypertension. T32HL160529, R00HL153686 This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.