Chronic emetine treatment ameliorates blood pressure development in spontaneously

Nearly fifty percent of all US adults have hypertension which greatly increases the risk of other comorbidities and is a significant contributor to all-cause mortality. 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. There is a need to better understand the mechanisms involved in the onset and progression of hypertension. Previous work found that reduced Golgi calcium stores were associated with altered smooth muscle cell (SMC) calcium signaling, impaired contractility, reduced arterial remodeling, and lower diastolic blood pressure in a model of salt sensitive hypertension. Emetine is a compound found in the ipecac plant that has been used for decades for its emetic and antiparasitic properties. While its use has been mostly discontinued due to cardiotoxicity at high doses, it has received renewed interest for antiviral and anticarcinogenic properties at lower, nontoxic, doses. A group studying pulmonary arterial hypertension (PAH) utilized emetine in a rat model of PAH and observed that chronic treatment reduced remodeling in pulmonary arteries and reduced several inflammatory and proliferative proteins. Altogether, this data indicates that disruption of lumenal Golgi calcium stores may affect vascular remodeling and ameliorate blood pressure development, which led us to our hypothesis that chronic emetine treatment would ameliorate systemic hypertension. To test this, we surgically implanted spontaneously hypertensive rats (SHRs) with telemeters and treated them with emetine (0.05 mg/kg bodyweight) or vehicle by oral gavage every day. Blood pressure measurements revealed that emetine treated rats had reduced mean arterial pressure compared to the vehicle group (151 ± 4 vs 143 ± 2 mmHg) and there were no differences in bodyweight, kidney weight, or heart weight. Tissue histology analysis revealed that emetine did not result in kidney or heart damage at this dosage and time course, and there was no effect on aorta remodeling. To look at potential acute effects of emetine application, we performed wire myography on rat aortas. We observed that acute emetine application had no effect on aortas in basal conditions though in contracted vessels that were pretreated with phenylephrine it resulted in significant dose-depended relaxation, with an EC50 of around 100 µM. Furthermore, the presence of L-NAME did not affect the relaxation induced by emetine, suggesting the mechanism of action is likely endothelial-independent. 2-photon imaging of isolated mesenteric resistance arteries showed that chronic emetine treatment disrupts calcium signaling in ex vivo SMCs. Our initial data indicate that emetine may have beneficial effects on systemic hypertension, both through chronic and acute mechanisms, but further work is necessary to fully characterize its physiological effects and further uncover the underlying mechanisms. This abstract was presented at the American Physiology Summit 2026 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.