ROLE OF ARTERIAL TRPV1 CHANNELS IN ADRENERGIC SIGNALING

We previously demonstrated that intravenous administration of capsaicin, a TRPV1 agonist dose‐dependently increased mean arterial pressure (MAP) in control mice which was absent in TRPV1 null (TRPV1 (−/−) ) mice. We hypothesized that vascular TRPV1 channels may play a role in adrenergic signaling. Phenylephrine (PE: 2.5, 5 μg/kg) significantly increased MAP in control mice however responses were significantly attenuated in TRPV1 (−/−) mice, suggesting TRPV1 channels contribute to PE‐mediated vasoconstriction. Furthermore, TRPV1 inhibition with SB366791 (5 mg/kg) attenuated PE mediated increases in MAP in control mice confirming its involvement in adrenergic‐mediated vasoconstriction. PE dose response curves in pressurized murine mesenteric microvessels, demonstrated attenuated vasoconstriction in TRPV1 (−/−) compared to controls. PE induced increases in intracellular calcium concentrations in VSMCs isolated from aortas from both groups however responses were blunted in TRPV1 (−/−) mice. SB366791 blunted PE‐mediated calcium changes in VSMCs from controls, further supporting a role for TRPV1 in adrenergic signaling. Immunofluorescence of cryosected aortas detail TRPV1 expression in both endothelial and smooth muscle layer. Conclusion Vascular TRPV1 channels may contribute to adrenergic signaling which suggests a paradigm shift from current views of adrenergic signaling mechanisms.