Long-term effects of photobiomodulation therapy on blood pressure in obese rats induced by a high-fat diet.

The main cardiovascular disease risk associated with obesity is hypertension. The therapeutic use of photobiomodulation therapy (PBM) is suggested for the treatment of wound healing, osteoarthritis, and arterial diseases. However, few studies have measured how red laser (at 660 nm) acts over hypertension, and any of those studies used experimental obesity model. The aim of the study was an attempt to evaluate the long-term effect of PBM on systolic blood pressure in an animal model of obesity, induced by a high-fat diet (HFD). Our results indicate that PBM carried out 3 days a week was able to prevent the increase in blood pressure (133.75 ± 4.82 mmHg, n = 8) induced by a high-fat diet (150.00 ± 4.57 mmHg, n = 8; p < 0.05), restore nitric oxide levels (control: 31.7 ± 5.5 µM, n = 8; HFD + PBM: 29.9 ± 3.7 µM, n = 8 > HFD: 22.2 ± 2.9 µM, n = 8, p < 0.05), decrease lipoperoxidation (control: 1.65 ± 0.25 nM, n = 8; HFD + PBM: 2.05 ± 0.55 nM, n = 8 < HFD: 3.20 ± 0.47 nM, n = 8; p < 0.05), and improve endothelial function (pD2 control: 7.39 ± 0.08, n = 8 > pD2 HFD + PBM: 7.15 ± 0.07, n = 8 > HFD: 6.94 ± 0.07, n = 8; p < 0.05). Our results indicate that PBM prevents the elevation of blood pressure in an obese animal model by a mechanism that involves improvement of endothelial function through an antioxidant effect.

Chronic red laser treatment induces hypotensive effect in two-kidney one-clip model of renovascular hypertension in rat.

To evaluate whether the chronic effect of photobiomodulation therapy (PBM) on systolic arterial pressure (SAP) from two kidneys one clip (2 K-1C) hypertension animal models can cause a hypotensive effect. Serum levels of nitric oxide were also analyzed and the assessment of lipid peroxidation of the thoracic aorta artery. Male Wistar rats were used. Hypertensive animals (2 K-1C) with Systolic arterial pressure (SAP) greater than or equal to 160 mmHg were used. Systolic arterial pressure (SAP) was determined by the tail plethysmography technique. Normotensive (2 K) and hypertensive (2 K-1C) rats were treated to PBM for 4 weeks using a laser whose irradiation parameters were: red wavelength (λ) = 660 nm: operating continuously; 56 s per point (3 points) spot size = 0.0295 cm2; average optical power of 100 mW; energy of 5.6 J per point; irradiance of 3.40 W/cm2; fluency of 190 J/cm2 per point. The application was on the animals tails, at 3 different points simultaneously, in contact with the skin. To assess serum nitrite and nitrate (NOx) levels, blood collection was performed after chronic PBM treatment, 24 h after the last laser application. The evaluation of the lipid peroxidation of the thoracic aorta artery was performed by measuring the concentration of hydroperoxide by the FOX method. Chronic photobiomodulation therapy (PBM) by red laser (660 nm) can induce a hypotensive effect in 64% of 2 K-1C hypertensive animals, which we say responsive animals. There was no difference in serum NO levels 24 h after the last red laser application, between treated and non-treated groups. Aortic rings from 2 K-1C hypertensive animals present a higher lipid peroxidation. The chronic PBM treatment by red laser decreased aortic rings lipid peroxidation in hypertensive responsive groups, compared to control. our results indicate that chronic PBM made by red laser has an important hypotensive effect in renovascular hypertensive models, by a mechanism that involves decrease in oxidative stress from vascular beds.

Vascular Effects of the Fetal Hemoglobin Inducer Agent 3-(1,3-Dioxoisoindolin-2-yl) Benzyl Nitrate.

Vascular endothelium is a protective layer of cells lining the lumen of blood vessels that plays important roles by releasing factors responsible for controlling the vascular tone, regulating the expression of pro-inflammatory cytokines, and expressing adhesion molecules involved in vascular hemostasis. Imbalance of vascular properties leads to endothelial dysfunction (ED) and cardiovascular damage. Some diseases, such as sickle cell anemia, are characterized by ED with reduction in the levels of nitric oxide (NO). Previously, we have shown that the fetal hemoglobin inducer agent 3-(1,3-dioxoisoindolin-2-yl) benzyl nitrate (Lapdesf-4c) could act as NO donor, inhibiting platelet aggregation and reducing the inflammation associated with SCA. However, the vascular effect of this compound was not yet studied. Herein, we evaluated the effects of Lapdesf-4c in vascular reactivity experiments using aortic rings from male Wistar rats (300 g/90 days). We have found that Lapdesf-4c induced vasodilation in the presence (E+) or absence of endothelium (E-) with an average of EMax values of 101.8 ± 3.33% and 111.8 ± 3.21%. The mechanism of action was studied using 1H-[1,2,4]oxadiazolo[4,3-alpha]quinoxalin-1-one (ODQ), L-NG-nitroarginine methyl ester (L-NAME), and hydroxocobalamin. The EMax values for those pathways were hydroxocobalamin (30.6 ± 2.21%), ODQ (4.75 ± 0.51%), and L-NAME (109 ± 3.65), suggesting that Lapdesf-4c exhibits NO-dependent mechanisms. Lapdesf-4c was able to prevent angiotensin-induced ED after incubation of aorta rings for 1 h. We found based on the concentration-effect curve using acetylcholine (ACh) that pEC50 values for the control, Ang II, and combination of (Ang II + Lapdesf-4c) were 6.73, 6.46, and 7.15, respectively. In conclusion, Lapdesf-4c has emerged as a new drug candidate that can promote vasodilation and act as a protective agent against ED, being useful to prevent vascular damage.

Violet LED induces vasodilation in rat aortic rings by soluble guanylate cyclase-dependent mechanism and increases SOD activity.

We found several studies that have used the aortic rings as an experimental model, mainly for the testing of new drugs or new therapies that try to reverse or prevent endothelial dysfunction or characterize its mechanism of action in a biological system, creating the knowledge necessary to obtain the treatment of those several diseases, where many of these treatments involve photobiomodulation therapies. We also found numerous wavelengths represented by different colors of LASER or LED in which frequently, the mechanism of action in biological systems is unknown. This study has as main objective to investigate the effects of the Violet LED Light (405 nm) by using isolated aortic rings, looking for nitric oxide (NO) release, and evaluating if Violet LED Light can modulate the superoxide dismutase (SOD) activity. We performed a vascular reactivity study in isolated aortic rings from normotensive rats with a single LED application. Besides it, the rings were pre-incubated with soluble guanylate cyclase (sGC) inhibitor or endothelial NO synthase inhibitor and subsequently underwent the application of the Violet LED. The cell viability and nitric oxide release in cell culture of human umbilical codon vein cells (HUVEC) were analyzed. In the vascular reactivity experiment, we observed a peak of vasodilation when applying light to the aortic rings. The soluble guanylate cyclase inhibitor abolished the relaxation induced by the Violet LED Light. However, the NO synthase inhibitor did not modify the Violet LED effect. In an isolated system, we verified that the Violet LED Light can increase SOD activity. Our results suggest that Violet LED Light induces vasodilation by a mechanism dependent on sGC activation, and not by NOS activation, and part of this effect could be due to the increase of SOD activity.

Multidrug-resistant protein inhibitor and phosphodiesterase inhibitor potentiate the vasodilator effect induced by photobiomodulation in isolated aortic rings.

A previous work indicates that the red LASER (660 nm) induces vascular relaxation by nitric oxide (NO)-dependent mechanism. NO activates soluble guanylate cyclase (sGC) which produces cGMP, the main effector in the vasodilation pathway. An interesting pharmacological strategy is to control the levels of intracellular cGMP, preventing its efflux (with multidrug-resistant protein blockers, such as MK-571), or preventing its degradation (such as sildenafil, which inhibits the enzyme responsible for cGMP degradation, the phosphodiesterase-5 PDE5). This study aimed to look for pharmacological strategies to improve vasodilation LASER effect in normotensive and hypertensive rats (L-NAME model). The vascular reactivity study was performed in isolated aortic rings from normotensive and hypertensive rats, with a single LASER application and sodium nitroprusside (SNP) treatment. In aortic rings from normotensive rats, MK-571 and sildenafil potentiated the relaxation induced by LASER, compared to control. The vasodilation induced by SNP was potentiated by MK-571 and sildenafil, compared to control. In aortic rings from hypertensive rats, vasodilation effect induced by LASER and by SNP was potentiated just by MK-571, compared to control, with no potentiation by sildenafil. In addition, it was seen that the withdrawal of nitric oxide stocks carried out by L-cysteine is capable of being reversed with the use of the SNP. The results support the evidence that the vasodilation induced by red LASER is potentiated by MK-571 and sildenafil in aortic rings from normotensive rats. However, in aortic rings from L-NAME hypertensive rats, the potentiation in vasodilation was induced just by MK-571.