Toll‐like receptor 2 activation increases adrenergic sensitivity in mesenteric resistance vessels of rats

Abstract

Toll-like receptors (TLRs) are pattern recognition receptors of the innate immune system that recognize microbial pathogens as well as endogenous damage-associated molecular patterns (DAMPS). TLR2 plays a role in cardiovascular diseases (CVD) such as atherosclerosis and heart failure, but its role in vascular function is unknown. We hypothesized that TLR2 activation would increase contractile responses in resistance arteries. We used second order mesenteric arteries from 15-week old Sprague Dawley rats in a small vessel wire myograph. Concentration response curves to norepinephrine (NE; 10−9–10−4 M) were performed in vessels incubated with and without TLR2 agonist Pam3CSK4 [(P3C4); 300ng/mL; 35′ prior incubation], as well as a combination of P3C4 and TLR2 antibody (1 μg/mL; 35′ prior incubation). The sensitivity of the vessels to NE was increased in vessels treated with P3C4 (LogEC50: 6.13± 0.08) compared to control (LogEC50: 5.55± 0.09), and this increase was attenuated by anti-TLR2 (LogEC50: 5.53± 0.05) (p<.05). These results indicate that TLR2 activation increases the sensitivity to adrenergic stimuli in resistance vessels, potentially leading to vascular dysfunction and contributing to CVD such as hypertension.