TRPV1 Contributes to Modulate the Nitric Oxide Pathway and Oxidative Stress in the Isolated and Perfused Rat Heart during Ischemia and Reperfusion

Abstract

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.

Evolving Strategies for Use of Phytochemicals in Prevention and Long-Term Management of Cardiovascular Diseases (CVD)

“…Experiments to fully characterize this effect are ongoing. Results at the time of this writing are particularly encouraging since the robust suppression of inflammatory tissue damage has been demonstrated for turmeric [ 46 ], ginger [ 47 , 48 ], capsicum/capsaicin—in red pepper [ 49 , 50 ], paprika [ 51 , 52 ], and nutmeg [ 53 , 54 , 55 ] as described in Section 2 of this report. In summary, the research described here describes the current understanding of cardiovascular diseases and approaches to its management, and explores novel strategies for the use of GRAS natural medical materials to potentiate clinical efficacy and reduce the toxicity of currently used therapies for CVDs.…”

“…It is nevertheless interesting to note that, during the past decade, the personal utilization of risk reduction strategies available through public education has resulted in some abatement of mortality rates in affluent societies. This includes, prominently, an awareness of the benefits to general health of the dietary intake of polyphenols, especially in flavonoid-rich foods, and flavorings such as the spices described in the present report [ 5 , 6 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 ].…”

“…The findings revealed by the investigations described in this report are particularly exciting since they suggest a means of expanding and refining the known health benefits of foodstuffs that are widely available at low cost. Particularly exciting are reports showing the strong ability of commonly used spice flavorings to reduce the severity of cardiovascular ischemia/reperfusion-related symptoms, notably, turmeric [ 46 ], ginger [ 47 , 48 ], capsicum/capsaicin—in red pepper [ 49 , 50 ]—including paprika [ 51 , 52 ] and nutmeg [ 53 , 54 , 55 ]. Each of these spices contain bioactive compounds that interact to exhibit very potent anti-inflammatory synergy, with high potential for the long-term clinical management of CVD and many other disorders at minimal cost and with no adverse side effects.…”

Liquiritin: A natural flavonoid with potential cardiovascular protection

“…We searched the targets related to the cardiovascular diseases and discovered their protein data bank (PDB) structures. Major targets closely associated with cardiovascular diseases are TLR4 (Zhang et al, 2022), Kelchlike ECH-associated protein 1 (Keap-1) (Han et al, 2022), AMPK (Wu and Zou, 2020), phosphoinositide 3-kinase (PI3K; Qin et al, 2021), Janus kinase 1 (JAK-1; Shen et al, 2019), NLRP3 (Wang et al, 2020), glycogen synthase kinase-3 beta (GSK3β; Zeng et al, 2019), p38 mitogen-activated protein kinase (p38 MAPK; Tang et al, 2022), extracellular signal-regulated kinase (ERK; Gallo et al, 2019), and transient receptor potential vanilloid 1 (TRPV1; Castrejón-Téllez et al, 2022). Therefore, these targets were selected for docking with liquiritin so as to find its main target.…”

Garlic prevents the oxidizing and inflammatory effects of sepsis induced by bacterial lipopolysaccharide at the systemic and aortic level in the rat. Role of trpv1

“…We have recently published the effects of activation of TRPV1 with capsaicin on olecules that conform the NO pathway, molecules inducing oxidative stress and molecules that produce cell damage in rat aorta and in heart [ 14 , 15 ]. Here we study whether garlic pretreatment (to activate TRPV1) can counteract the inflammatory and oxidative effects of Escherichia coli LPS-induced sepsis at the systemic and aortic level in Wistar rats.…”