TRPV1 Contributes to Modulate the Nitric Oxide Pathway and Oxidative Stress in the Isolated and Perfused Rat Heart during Ischemia and Reperfusion.
Vicente Castrejón-TéllezLeonardo Del Valle-MondragonIsrael Pérez-TorresVerónica Guarner-LansGustavo Pastelín-HernándezAngélica Ruiz-RamírezJulieta Anabell Díaz-JuárezElvira Varela-LópezVíctor Hugo Oidor-ChanAlvaro Vargas-GonzálezRaúl Martínez-MemijePedro Flores-ChávezBruno León-RuízSergio Arriaga-CarrilloJuan Carlos Torres-NarváezPublished in: Molecules (Basel, Switzerland) (2022)
The transient vanilloid receptor potential type 1 (TRPV1) regulates neuronal and vascular functions mediated by nitric oxide (NO) and by the calcitonin gene-related peptide (CGRP). Here, we study the participation of TRPV1 in the regulation of myocardial injury caused by ischemia-reperfusion and in the control of NO, tetrahydrobiopterin (BH4), the cGMP pathway, CGRP, total antioxidant capacity (TAC), malondialdehyde (MDA) and phosphodiesterase-3 (PDE-3). Isolated hearts of Wistar rats perfused according to the Langendorff technique were used to study the effects of an agonist of TRPV1, capsaicin (CS), an antagonist, capsazepine (CZ), and their combination CZ+CS. The hearts were subjected to three conditions: (1) control, (2) ischemia and (3) ischemia-reperfusion. We determined cardiac mechanical activity and the levels of NO, cGMP, BH4, CGRP, TAC, MDA and PDE-3 in ventricular tissue after administration of CS, CZ and CZ+CS. Western blots were used to study the expressions of eNOS, iNOS and phosphorylated NOS (pNOS). Structural changes were determined by histological evaluation. CS prevented damage caused by ischemia-reperfusion by improving cardiac mechanical activity and elevating the levels of NO, cGMP, BH4, TAC and CGRP. TRPV1 and iNOS expression were increased under ischemic conditions, while eNOS and pNOS were not modified. We conclude that the activation of TRPV1 constitutes a therapeutic possibility to counteract the damage caused by ischemia and reperfusion by regulating the NO pathway through CGRP.
Keyphrases
- nitric oxide
- nitric oxide synthase
- oxidative stress
- neuropathic pain
- cerebral ischemia
- heart failure
- hydrogen peroxide
- acute myocardial infarction
- physical activity
- gene expression
- spinal cord injury
- risk assessment
- protein kinase
- genome wide
- breast cancer cells
- spinal cord
- ischemia reperfusion injury
- subarachnoid hemorrhage
- transcription factor
- blood brain barrier
- cell death
- endoplasmic reticulum stress