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Characterization of the hypotensive effect by photobiomodulation in different hypertension animal models and pharmacological strategies to enhance this effect

Abstract

Endothelial dysfunction is characterized primarily by the decreased ability of endothelial cells to release nitric oxide (NO), which is an important physiological modulator of vascular tone, inhibits platelet aggregation, decreases adhesion molecule expression, decreases proliferation of vascular smooth muscle cells, and has an important anti-inflammatory effect; this effect is due to the activation of PPARg receptors, and inhibition of NF-kB. Because it is a radical species, NO reacts quickly with other molecules with unpaired electrons, being extremely unstable under physiological conditions. Superoxide anion (O2-) decreases NO bioavailability and also activates NF-kB, which is an important proinflammatory transcription factor; which has been found activated in cells of the cardiovascular system in the presence of cardiovascular diseases, including hypertension. Thus, elevation of NO concentration, as well as O2- reduction in the cardiovascular system, may be a strategy to induce a drop in blood pressure, an improvement in endothelial function and an inflammatory profile. This modulation can be induced by the use of photobiomodulation, also known as low level LASER therapy (LLLT). Results from our laboratory indicate that the red LASER (660 nm) is capable of inducing NO release of vascular tissue, as well as inducing a drop in blood pressure in hypertensive animals. Data from the literature indicate that this LASER range is capable of decreasing O2- concentration, as well as reducing systemic inflammation. The increase of NO may be due to the conversion of nitrite (NO2-) to NO, which makes it possible to enhance the effect of LASER application by the association with nitrite. Another pharmacological strategy that can potentiate the effect of LASER is by blocking multidrug resistance proteins (MRP). MRPs are able to delivering cyclic guanosine monophosphate (cGMP) to the extracellular medium. Considering that the main target of NO is the soluble guanylate cyclase enzyme (GCs), which catalyzes the exit of two phosphate groups from the guanosine triphosphate (GTP) molecule, resulting in the production of cGMP, inhibition of cGMP efflux by blocking of MRPs may potentiate the effect of LASER. Thus, the hypothesis of this project is that the red LASER (660nm) is capable of improving endothelial function, inducing blood pressure drop in different animal models, as well as potentiate these effects in the presence of nitrite and/or MPRs blocker. Therefore, the main objective of this project will be to test our hypothesis, as well as characterize the effects of photobiomodulation, and its possible potentiation by pharmacological intervention by the association with nitrite and/or MPRs blocker. (AU)

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Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
OLIVEIRA DE MORAES, LUIS HENRIQUE; TERRONI, BARBARA; DA SILVA MAYER, NAYARA FORMENTON; RODRIGUES, GERSON JHONATAN. Multidrug-resistant protein inhibitor and phosphodiesterase inhibitor potentiate the vasodilator effect induced by photobiomodulation in isolated aortic rings. Lasers in Medical Science, JUL 2021. Web of Science Citations: 0.
DE MORAES, T. F.; FILHO, J. C. C.; OISHI, J. C.; ALMEIDA-LOPES, L.; PARIZOTTO, N. A.; RODRIGUES, G. J. Energy-dependent effect trial of photobiomodulation on blood pressure in hypertensive rats. Lasers in Medical Science, OCT 2019. Web of Science Citations: 0.

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