| Autor: |
Rivera-Mancilla E; Division of Vascular Medicine and Pharmacology, Department of Internal Medicine, Erasmus University Medical Center Rotterdam, P.O. Box 2040, 3000 CA Rotterdam, The Netherlands., Al-Hassany L; Division of Vascular Medicine and Pharmacology, Department of Internal Medicine, Erasmus University Medical Center Rotterdam, P.O. Box 2040, 3000 CA Rotterdam, The Netherlands., Marynissen H; Department of Pharmaceutical and Pharmacological Sciences, Center for Clinical Pharmacology, KU Leuven, 300 Leuven, Belgium., Bamps D; Department of Pharmaceutical and Pharmacological Sciences, Center for Clinical Pharmacology, KU Leuven, 300 Leuven, Belgium., Garrelds IM; Division of Vascular Medicine and Pharmacology, Department of Internal Medicine, Erasmus University Medical Center Rotterdam, P.O. Box 2040, 3000 CA Rotterdam, The Netherlands., Cornette J; Department of Obstetrics and Fetal Medicine, Erasmus University Medical Center Rotterdam, P.O. Box 2040, 3000 CA Rotterdam, The Netherlands., Danser AHJ; Division of Vascular Medicine and Pharmacology, Department of Internal Medicine, Erasmus University Medical Center Rotterdam, P.O. Box 2040, 3000 CA Rotterdam, The Netherlands., Villalón CM; Department of Pharmacobiology, Cinvestav-Coapa, Mexico City C.P. 14330, Mexico., de Hoon JN; Department of Pharmaceutical and Pharmacological Sciences, Center for Clinical Pharmacology, KU Leuven, 300 Leuven, Belgium., MaassenVanDenBrink A; Division of Vascular Medicine and Pharmacology, Department of Internal Medicine, Erasmus University Medical Center Rotterdam, P.O. Box 2040, 3000 CA Rotterdam, The Netherlands. |
| Abstrakt: |
Transient receptor potential (TRP) channels are pivotal in modulating vascular functions. In fact, topical application of cinnamaldehyde or capsaicin (TRPA1 and TRPV1 channel agonists, respectively) induces "local" changes in blood flow by releasing vasodilator neuropeptides. We investigated TRP channels' contributions and the pharmacological mechanisms driving vasodilation in human isolated dermal arteries. Ex vivo studies assessed the vascular function of artery segments and analyzed the effects of different compounds. Concentration-response curves to cinnamaldehyde, pregnenolone sulfate (PregS, TRPM3 agonist), and capsaicin were constructed to evaluate the effect of the antagonists HC030031 (TRPA1); isosakuranetin (TRPM3); and capsazepine (TRPV1). Additionally, the antagonists/inhibitors olcegepant (CGRP receptor); L-NAME (nitric oxide synthase); indomethacin (cyclooxygenase); TRAM-34 plus apamin (K + channels); and MK-801 (NMDA receptors, only for PregS) were used. Moreover, CGRP release was assessed in the organ bath fluid post-agonist-exposure. In dermal arteries, cinnamaldehyde- and capsaicin-induced relaxation remained unchanged after the aforementioned antagonists, while PregS-induced relaxation was significantly inhibited by isosakuranetin, L-NAME and MK-801. Furthermore, there was a significant increase in CGRP levels post-agonist-exposure. In our experimental model, TRPA1 and TRPV1 channels seem not to be involved in cinnamaldehyde- or capsaicin-induced relaxation, respectively, whereas TRPM3 channels contribute to PregS-induced relaxation, possibly via CGRP-independent mechanisms. |
