Arterial Dilation by Phototherapy

Cardiovasc Res.  2009 Sep 1;83(4):785-92. Epub 2009 May 14.

Low-level laser irradiation inhibits abdominal aortic aneurysm progression in apolipoprotein E-deficient mice.

Gavish L, Rubinstein C, Bulut A, Berlatzky Y, Beeri R, Gilon D, Gavish L, Harlev M, Reissman P, Gertz SD.

Source

Department of Anatomy, The Hebrew University-Hadassah Medical School, PO Box 12272, Jerusalem 91120, Israel.

Abstract

AIMS:

Increased early detection of abdominal aortic aneurysm (AAA) and the severe complications of its current treatment have emphasized the need for alternative therapeutic strategies that target pathogenetic mechanisms of progression and rupture. Recent in vitro studies from our laboratory have shown that low-level laser irradiation (LLLI) (780 nm) modifies cellular processes fundamental to aneurysm progression. The present study was designed to determine whether LLLI retards the progression of suprarenal AAA in vivo.

METHODS AND RESULTS:

High-frequency ultrasonography (0.01 mm resolution) was used to quantify the effect of LLLI on aneurysmatic aortic dilatation from baseline to 4 weeks after subcutaneous infusion of angiotensin II by osmotic minipumps in the apolipoprotein E-deficient mouse. At 4 weeks, seven of 15 non-irradiated, but none of the 13 LLLI, mice had aneurysmal dilatation in the suprarenal aneurysm-prone segments that had progressed to >or=50% increase in maximal cross-sectional diameter (CSD) over baseline (P = 0.005 by Fisher’s exact test). The mean CSD of the suprarenal segments (normalized individually to inter-renal control segments) was also significantly lower in irradiated animals (LLLI vs. non-irradiated: 1.32 +/- 0.14 vs. 1.82 +/- 0.39, P = 0.0002 by unpaired, two-tailed t-test) with a 94% reduction in CSD at 4 weeks compared with baseline. M-mode ultrasound data showed that reduced radial wall velocity seen in non-treated was significantly attenuated in the LLLI mice, suggesting a substantial effect on arterial wall elasticity.

CONCLUSION:

These in vivo studies, together with previous in vitro studies from this laboratory, appear to provide strong evidence in support of a role for LLLI in the attenuation of aneurysm progression. Further studies in large animals would appear to be the next step towards testing the applicability of this technology to the human interventional setting.

J Hypertens.  2009 Aug;27(8):1631-40.

Light-induced vs. bradykinin-induced relaxation of coronary arteries: do S-nitrosothiols act as endothelium-derived hyperpolarizing factors?

Batenburg WW, Kappers MH, Eikmann MJ, Ramzan SN, de Vries R, Danser AH.

Source

Department of Internal Medicine, Division of Pharmacology, Vascular and Metabolic Diseases, Erasmus Medical Center, Rotterdam 3015 GE, The Netherlands.

Abstract

BACKGROUND:

Light-induced relaxation depends on S-nitrosothiols. S-Nitrosothiols may also serve as endothelium-derived hyperpolarizing factors, mediating the relaxant response of porcine coronary arteries (PCAs) to bradykinin. Here we compared the mechanism of light-induced and bradykinin-induced PCA relaxation.

METHODS:

PCAs were mounted in organ baths in the dark, preconstricted and exposed to polychromatic light (5 min) or 100 nmol/l bradykinin.

RESULTS:

Light relaxed PCAs by maximally 71 +/- 1%. S-Nitrosothiol depletion abolished this relaxation. Relaxations diminished following repetitive light exposures, particularly if the dark periods between the light exposures were less than 10 min, and increased following endothelium removal or nitric oxide synthase blockade with N(omega)-nitro-L-arginine methyl ester (L-NAME), despite the prevention of guanosine-3′,5′-cyclic monophosphate generation by the latter two procedures. Thus, reloading of the storage pools occurs in the dark, endothelial nitric oxide inhibits this process and photorelaxation does not depend on guanosine-3′,5′-cyclic monophosphate. Bradykinin relaxed PCAs by 69 +/- 3%. The nitric oxide scavenger hydroxocobalamin and the Na+-K+ ATPase inhibitor ouabain abolished the responses to bradykinin and light. The guanylyl cyclase inhibitor 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one abolished the response to light, and, like L-NAME, blocked the response to bradykinin by more than 50%. On top of L-NAME, intermediate and small conductance Ca2+-dependent K+ channel (IKCa/SKCa) blockade further reduced the response to bradykinin and enhanced photorelaxation.

CONCLUSION:

Photorelaxation depends on stored S-nitrosothiols and their release/synthesis is negatively affected by endothelial nitric oxide and IKCa/SKCa. S-Nitrosothiols activate endothelial IKCa/SKCa and, via guanylyl cyclase, smooth muscle Na+-K+ ATPase. Thus, they possess all properties of a bradykinin-induced endothelium-derived hyperpolarizing factor.

Br J Pharmacol.  2003 Mar;138(5):932-40.

A photosensitive vascular smooth muscle store of nitric oxide in mouse aorta: no dependence on expression of endothelial nitric oxide synthase.

Andrews KL, McGuire JJ, Triggle CR.

Source

Smooth Muscle Research Group, 3330 Hospital Dve, NW, University of Calgary, Calgary, Alberta, Canada, T2N 4N1.

Abstract

(1) Photorelaxation is the reversible relaxation of vascular smooth muscle (VSM) when irradiated with ultraviolet (UV) light resulting from the release of nitric oxide (NO). In this study we characterize the involvement of endothelial nitric oxide synthase (eNOS) in the photorelaxation response of thoracic aorta from endothelial NOS deficient (-/-) and control (C57BL/6j) mice. (2) Cirazoline contracted aortae were repeatedly exposed to 30 s of UV light every 3-4 min. Equal levels of photorelaxation (45+/-2%; n=34) was observed in both strains. (3) 1H-[1,2,4]-oxadiazolo[4,3-a]quinoxalin-1-one (ODQ), K(+), 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (c-PTIO), 4-aminopyridine (4-AP) and ethacrynic acid significantly reduced the photorelaxation response. In C57BL/6j mice diethyldithiocarbamate (DETCA) also reduced photorelaxation. (4) Control endothelium-intact and -denuded aorta and L-NAME (100 micro M) treated and untreated eNOS (-/-) aortae were repeatedly exposed to UV light for 5 min every 10 min until no photorelaxation response was observed. After 1 h of rest in the dark the vessels showed between 30-70% recovery of the photorelaxation response indicating regeneration of the store in the absence of the endothelium and eNOS. (5) The results of this study suggest that photorelaxation in mouse aorta VSM results from the release of NO from a stable store of RSNOs, which activates soluble guanylate cyclase (sGC), leading to cGMP-dependent relaxation that is partially mediated by an increase in K(V) channel activation and hyperpolarization. In addition, the eNOS isoform is not essential for the formation of the photorelaxation store and a non-NOS source of NO may be involved in the maintenance of this store.

Lasers Surg Med.  2000;27(5):427-37.

Effects of near-infrared low-level laser irradiation on microcirculation.

Maegawa Y, Itoh T, Hosokawa T, Yaegashi K, Nishi M.

Source

Department of Anesthesiology, Kyoto Prefectural University of Medicine, Japan.

Abstract

BACKGROUND AND OBJECTIVE:

Recently, there has been an increase in the clinical application of low-level laser irradiation (LLLI) in various fields. The present study was conducted to explore the effects of LLLI on microcirculation.

STUDY DESIGN/MATERIAL AND METHODS:

We investigated the effects of LLLI on rat mesenteric microcirculation in vivo, and on cytosolic calcium concentration ([Ca2+]i) in rat vascular smooth muscle cells (VSMCs) in vitro.

RESULTS:

LLLI caused potent dilation in the laser-irradiated arteriole, which led to marked increases in the arteriolar blood flow. The changes were partly attenuated in the initial phase by the superfusion of 15 microM L-NAME, but they were not affected by local denervation. Furthermore, LLLI caused a power-dependent decrease in [Ca2+]i in VSMCs.

CONCLUSION:

The circulatory changes observed seemed to be mediated largely by LLLI-induced reduction of [Ca2+]i in VSMCs, in addition to the involvement of NO in the initial phase.