Investig Clin Urol.  2016 May;57(3):215-220. 10.4111/icu.2016.57.3.215.

Light-controlled relaxation of the rat penile corpus cavernosum using NOBL-1, a novel nitric oxide releaser

• Hotta Y
• Ieda N
• Fukamoto A
• Kataoka T
• Kawade Y
• Maeda Y
• Nakagawa H
• Kimura K

• KMID: 2426497
• DOI: http://doi.org/10.4111/icu.2016.57.3.215

Abstract

PURPOSE
To investigate whether relaxation of the rat penile corpus cavernosum could be controlled with NOBL-1, a novel, light-controllable nitric oxide (NO) releaser.
MATERIALS AND METHODS
Fifteen-week-old male Wistar-ST rats were used. The penile corpus cavernosum was prepared and used in an isometric tension study. After noradrenaline (10-5 M) achieved precontraction, the penile corpus cavernosum was irradiated by light (470-500 nm) with and without NOBL-1 (10-6 M). In addition, we noted rats' responses to light with vardenafil (10-6 M), a phosphodiesterase-5 (PDE-5) inhibitor. Next, responses to light in the presence of a guanylate cyclase inhibitor, ODQ (1H-[1,2,4] oxadiazolo[4,3-a]quinoxalin-1-one) (10-5 M), were measured. All measurements were performed in pretreated L-NAME (10-4 M) conditions to inhibit endogenous NO production.
RESULTS
Corpus cavernosal smooth muscle, precontracted with noradrenaline, was unchanged by light irradiation in the absence of NOBL-1. However, in the presence of NOBL-1, corpus cavernosal smooth muscle, precontracted with noradrenaline, relaxed in response to light irradiation. After blue light irradiation ceased, tension returned. In addition, the light response was obviously enhanced in the presence of a PDE-5 inhibitor.
CONCLUSIONS
This study showed that rat corpus cavernosal smooth muscle relaxation can be light-controlled using NOBL-1, a novel, light sensitive NO releaser. Though further in vivo studies are needed to investigate possible usefulness, NOBL-1 may be prove to be a useful tool for erectile dysfunction therapy, specifically in the field of penile rehabilitation.

Keyword

Light; Nitric oxide; Penis; Rehabilitation; Smooth muscle

MeSH Terms

Animals
Guanylate Cyclase/antagonists & inhibitors
Male
Muscle Relaxation/*drug effects/radiation effects
Muscle, Smooth/drug effects/radiation effects
Nitric Oxide/*physiology
Nitric Oxide Donors/*pharmacology
Oxadiazoles/pharmacology
Penis/*drug effects/physiology/radiation effects
Phosphodiesterase 5 Inhibitors/pharmacology
Photic Stimulation/*methods
Quinoxalines/pharmacology
Rats, Wistar
Vardenafil Dihydrochloride/pharmacology

Figure

• 

  Fig. 1 Structure of NOBL-1.

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  Fig. 2 Evaluation system. (A) This work was performed in a dark room. White arrows represent the light source. (B) Penile tissue in light-irradiated organ bath. (C) Pattern diagram of evaluation system. Light was irradiated from outside the organ bath.

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  Fig. 3 Corpus cavernosum's response to light irradiation without (left) and with NOBL-1 (right). The yellow line represents light irradiation: short width, 15 seconds; long width, 30 seconds. NA, noradrenaline (10-5 M); NOBL-1 (10-6 M).

• 

  Fig. 4 Corpus cavernosum's response to light irradiation with NOBL-1 and vardenafil. The yellow line represents light irradiation: short width, 15 seconds; long width, 30 seconds. Var, vardenafil (10-6 M); NA, noradrenaline (10-5 M); NOBL-1 (10-6 M).

• 

  Fig. 5 Analysis of relaxing response to light irradiation. Relaxing response to light irradiation without NOBL-1 (white column), with NOBL-1 (gray column), and with NOBL-1 under vardenafil treatment (black column). Var, vardenafil, n=4, *p<0.05, **p<0.01.

• 

  Fig. 6 Corpus cavernosum's response to light irradiation with NOBL-1 and ODQ, a GC inhibitor. The yellow line represents light irradiation: short width, 15 seconds; long width, 30 seconds. ODQ, 1H-[1,2,4] oxadiazolo[4,3-a]quinoxalin-1-one (10-5 M); NOBL-1 (10-6 M).

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