Role of the transient receptor potential vanilloid-1 (TRPV1) in the development of hydrogen chloride (HCl)-induced vasomotor response in isolated rodent carotid arteries.

Ivic, Ivan and Pákai, Eszter and Solymár, Margit and Koller, Ákos and Garami, András (2014) Role of the transient receptor potential vanilloid-1 (TRPV1) in the development of hydrogen chloride (HCl)-induced vasomotor response in isolated rodent carotid arteries. In: Joint Meeting of the Federation of European Physiological Societies (FEPS) and the Hungarian Physiological Society, 2014. augusztus 27-30., Budapest.

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Abstract

It was shown earlier that acidic products released during anaerobic tissue metabolism are involved in the regulation of local blood flow. However, the mechanism, through which reductions of local pH evoke the change in vascular tone, is not fully elucidated. Among TRP channels located on vascular elements, TRPV1 plays an important role in sensing of environmental changes (e.g., pH, temperature, etc.). In the present study we hypothesized that TRPV1, which is abundantly expressed in the vascular wall and can be activated by acidic stimuli, plays a role in the vascular responses to low pH. Carotid arteries were isolated from Wistar rats, from mice genetically lacking TRPV1 channels (KO) and from wild-type mice. Isometric wall tension was measured with a myograph. Vessels were precontracted with 10-5 M phenylephrine (PhE), then isometric changes were measured in response to increasing concentrations of HCl (10-6–10-3 M). Functional integrity of the vessels (endothelium-dependent and -independent relaxation) was verified after each experiment. In rat carotid arteries, PhE caused a significant (~5 mN) isometric contraction, and addition of HCl caused dose-dependent relaxation, which was significant already at 10-6 M (-0.3±0.0 mN, p <0.05), and reached a maximum of -1.4±0.1 mN at 10-3 M. Capsaicin elicited significant contractions in carotid arteries isolated from wild-type mice, whereas it was ineffective in that of TRPV1 KO mice, confirming the lack of functional TRPV1 channels. Interestingly, HCl (10-6–10-3 M) caused a significantly greater arterial relaxation in TRPV1 KO mice as compared to controls (p <0.05 for each concentration). Based on these results, we can conclude that acidic environment results in arterial relaxation, the magnitude of which is limited by TRPV1 channels and that changes in local pH contributes to regulation of vasomotor tone to maintain optimal tissue blood flow. Support: SROP-4.2.2.A-11/1/KONV-2012-0024: Complex examination, SROP-4.2.2.A-11/1/KONV-2012-0017: New biomarkers, Hungarian National Scientific Research Found K108444 (AK), PD105532 (AG), Janos Bolyai Research Fellowship from Hungarian Academy of Sciences (AG).

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