Dexmedetomidine helps to modulate specific inflammatory reactions in pulmonary arterial hypertension (PAH) and may be useful as a new therapeutic agent, according to a study published in the Journal of Pharmacology and Experimental Therapeutics.
Extensive vascular remodeling occurs in PAH. This is a challenge in PAH therapeutics because most therapies are focused on vasodilation and do not significantly improve vascular remodeling.
Vascular remodeling is heavily driven by inflammation and inflammation is a key cause of PAH disease progression. In PAH, inflammatory cells assemble around pulmonary arterioles and inflammatory cytokines are more prevalent in the blood. Anti-inflammatory therapies used to treat comorbidities have been found to improve PAH symptoms.
Dexmedetomidine is a selective alpha-2 adrenergic receptor agonist that has strong anti-inflammatory properties. It has demonstrated a marked anti-inflammatory impact on acute lung injury in in vivo studies. The authors of the study hypothesized that the anti-inflammatory properties of dexmedetomidine may improve PAH outcomes.
Read more about PAH etiology
To test this theory, the research team injected rats with monocrotaline to simulate PAH-like physiological conditions. The rats were divided into 2 groups—1 received a continuous dexmedetomidine infusion at a rate of 2 μg/kg/h on day 14, while the other did not. On day 23, the surviving rats were euthanized and examined.
The results showed that the rats treated with dexmedetomidine had better right ventricular systolic pressure and improved survival compared to rats that received no treatment. In addition, the research team observed that dexmedetomidine had a suppressive effect on the muscularization of the pulmonary arterioles. Dexmedetomidine also had specific, measurable anti-inflammatory properties.
“In conclusion, [dexmedetomidine] improves [monocrotaline]-induced PAH in rats,” the authors of the study wrote. “We wish to verify the vascular effects of [dexmedetomidine] in future investigations.”
Yamaguchi Y, Hosokawa S, Haraguchi G, et al. The anti-inflammatory effects and clinical potential of dexmedetomidine in pulmonary arterial hypertension. J Pharmacol Exp Ther. Published online February 27, 2023. doi:10.1124/jpet.122.001399