Background: Hypertension is the most prevalent comorbidity of COVID-19 infection. This infection is caused by the severe acute respiratory syndrome coronavirus SARS-CoV-2. SARS-CoV-2 is a single-stranded RNA and could activate the endosomal Toll-like receptor 7 (TLR7), indicating a vital role of the receptor in its therapeutic target. Studies have reported that the lysosomotropic drug chloroquine has antihypertensive effects through its action on inhibiting the endosomal TLRs. Arbidol is a potential broad-spectrum antiviral used in the treatment of many viral infections including influenza. Arbidol prevents viral infection by interacting with aromatic acids; arbidol also binds to lipid membranes, altering the configuration of the cytoplasm or endosome. Wang et al., in 2020 reported that arbidol effectively inhibited the coronavirus SARS-CoV-2 in vitro by impeding viral attachment and release from the endolysosomes. Hypothesis: We hypothesized that arbidol would improve vascular reactivity in hypertension. Methods: We studied the effects of arbidol on the contractility of mesenteric resistance arteries (MRA) and aortas of male Wistar rats (20 weeks old, n=4) and spontaneously hypertensive rats (SHR) (20 weeks old, n=4) on a myograph by incubating the arterial rings with 10μM arbidol (Sigma, USA.) or vehicle (DMSO) for 30 mins. Statistical analysis was performed using nonlinear regression, and one- and two-way ANOVAs. Results: Arbidol (10 μM) impaired the contractile responses of MRA and aorta from normotensive and hypertensive rats to phenylephrine (PE). MRA Wistar: (pEC50 6.11 ± 0.15 vs 3.42 ± 0.38), SHR: (5.89 ± 0.19 vs 3.56 ± 0.19) and aorta Wistar: (pEC 50 7.49 ± 0.19 vs 5.97 ± 0.14), SHR (pEC50 7.14 ± 0.31 vs 4.41 ± 0.15). The arbidol-induced impaired contraction to PE was greater in the SHR aorta compared with the Wistar aorta. After washing out the drug, the arterial rings contracted to 120mM KCl at the same magnitude as the initial contraction to 120mM KCl. Conclusions: Our data demonstrate that arbidol impairs vascular contractile responses to α-adrenergic stimulation, with a greater response in the hypertensive rats. This indicates antihypertensive effects potentially through the regulation of TLR signaling.