0081 Leptin Induces Hypertension Acting in the Carotid Bodies: Possible involvement of Transient Receptor Potential Channels. (27th April 2018) - Shin, M
Abstract: Introduction: Obesity leads to cardiovascular morbidity and mortality acting via multiple mechanisms including hypertension and obstructive sleep apnea. Both obesity and obstructive sleep apnea increase levels of adipokine leptin. High levels of leptin have been implicated in increased sympathetic activity and the pathogenesis of hypertension. The carotid bodies (CB) express leptin receptor (LepR), but the mechanisms and consequences of leptin action in CB are unknown. We have previously demonstrated that leptin enhances carotid sinus nerve activity in response to hypoxia and this effect is abolished by non-selective blockers of transient receptor potential (TRP) channels (Shirahata et al., 2015). Therefore, we hypothesized that high levels of circulating leptin signal via LepR in CB leading to hypertension and this effect is abolished by TRP channel blockers. Methods: 1) LepR deficient db/db mice were implanted with telemetry; blood pressure was measured at baseline and after CB infection with adenovirus carrying the LepR gene ( Ad-LepR, n=5) or luciferase (control, Ad-Laz, n=6); 2) C57BL/6J mice (n=13) were implanted with telemetry for blood pressure monitoring at baseline, during leptin infusion (120ug/day for 3 days) with or without a TRP channel blocker. Results: 1) LepR expression in CB of db/db mice increased mean arterial pressure by 6 mmHg during the day and by 13 mmHg during at night ( p < 0.005 ), whereas control virus had no effect ( p=0.585 ). 2) In C57BL/6J mice, leptin infusion increased mean arterial pressure by 18.3 mmHg during the day ( p<0.01 ) and by 11.2 mm Hg at night ( p <0.005 ). TRP channel blockers completely abolished leptin-induced hypertension ( p < 0.001 ). Conclusion: Leptin increases blood pressure acting via LepR in the CB. Leptin-induced hypertension is abolished by TRP channel blockers suggesting that leptin may act via TRP channels. Support (If Any): HL133100, HL128970.