• The Journal of Korean Physical Therapy
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• 제15권2호
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• pp.146-156
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• 2003

Isolated rat thoracic aorta which is pharmacologically precontracted by phenylephrine induces photorelaxation when exposed to long wave length UV-light. The aim of the present study was to characterize the mechanism of UV-light induced by photorelaxation in the rat aorta. 1. UV light relaxed both endothelium-intact and -denuded rat aortic rings contracted by phenylephrine. The magnitude of relaxation on UV light was dependent on the exposure time and slightly greatly in endothelium-denuded rings than in endothelium-intact preparations. 2. L-NAME (10 nM - 100 $\mu$M) but not D-NAME completely inhibited the photorelaxation in a concentration dependent manner. 3. The UV-induced relaxation was inhibited by methylene blue (1 - 100 uM), and verapamil (100 nM), and removal of extracellular $Ca^{2+}$. In contrast, UV-light induced photorelaxation was potentiated by $N^{w}$-nitro-L-arginine (L-NNA) treatment. These results suggest that UV light-induced photorelaxation may be due to nitric oxide from exogenously administered L-arginine as well as endogenous nitric oxide donors such as amino acid and arginine derivatives

• 대한수의학회지
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• 제42권3호
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• pp.321-326
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• 2002

The effect of nitric oxide synthase(NOS) inhibita, $N^G$-nitro-L-arginine-methyl ester(L-NAME) and prostanoid synthesis inhibiter, indomethacin on the photorelaxation, when was exposed to the long-wave length UV-light, was examined on the precontraction by the phenylephrine in the isolated pig renal artery. 1. UV-light relaxed both with-endothelium and without-endothelium in the pig renal arterial ring contracted by the phenylephrine. The magnitude of photorelaxation was dependent on the exposure time for UV-light. 2. UV-Iight induced relaxation was inhibited by L-NAME and indomethacin on the precontraction by the phenylephrine in the isolated pig renal artery. 3. UV-Iight induced relaxation was inhibited by methylene blue on the precontraction by the phenylephrine in the isolated pig renal artery. These results suggest that UV-light induced photorelaxation may be due to cGMP involved both nitric oxide and prostanoid on the precontraction by the phenylephrine in the isolated pig renal artery.

• Biomolecules & Therapeutics
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• 제2권2호
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• pp.136-140
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• 1994

To prove the hypothesis that NO- and N $O_2$-carrying molecules potentiate photorelaxation by generating NO, investigation was carried out using isolated rabbit and human corpus cavernosum. Corporal smooth muscle, in the presence or absence of endothelium, relaxed only slightly upon ultraviolet light (366 nm) irradiation. But, NO-and/or N $O_2$-containing compounds such as streptozotocin and $N^{G}$-nitro-L-arginine methyl ester significantly (p<0.01) enhanced photorelaxation in this tissue. In addition, $N^{G}$-nitro-D-arginine methyl ester, known to lack inhibitory action on NO synthase, showed concentration-dependent potentiation of the photorelaxation. Oxygen radical generating system via copper＋ascorbic acid and guanylate cyclase inhibitor, methylene blue, significantly (p<0.05) inhibited the streptozotocin-potentiated photorelaxation. Nitrite was accumulated by photolysis of streptozotocin, $N^{G}$-nitro-L-arginine methyl ester and $N^{G}$-nitro-D-arginine methyl ester, in a concentration and exposure time dependent manner. These observations indicate that NO is a potent relaxant of rabbit and human corpus cavernosum and further support the hypothesis that NO is released by photolysis from NO- and N $O_2$-carrying molecules.lecules.

• Biomolecules & Therapeutics
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• 제3권1호
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• pp.58-62
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• 1995

We investigated whether nitric oxide (NO) may serve a role in bladder function by immunohistochemical analysis of the distribution of intrinsic NADPH-diaphorase and functional study of isometric tension recordings via a photo-induced adequate nitric oxide (PIANO) generating system using rat bladder. Results suggest that a small number of NADPH-diaphorase-positive perikarya are present within the bladder wall and within adjacent small ganglia. Furthermore, NADPH-diaphorase-positive nerve fibers were observed in the adventitial and muscular layers, subjacent to the urothelium and perivascular fibers. Rat bladder strips precontracted with 3$\mu$M carbachol were reversibly relaxed upon NO generation by UV irradiation. PIANO-mediated relaxation was sensitive to oxygen free radicals. In addition, tissue cGMP levels were increased by the PIANO generating system and elevated cGMP levels were decreased by pretreatment of guanylate cyclase inhibitor, methylene blue. These results indicate that NO may serve a role in modulating bladder tone in the rat.

• Biomolecules & Therapeutics
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• 제3권2호
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• pp.149-153
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• 1995

Nitric oxide (NO) has been regarded as one of the neurotransmitters of nonadrenergic, noncholinergic (NANC) nerve stimulation in rabbit corpus cavernosum, rat gastric fundus and human intestine. PIANO (photo-induced adequate nitric oxide) is a very useful tool to investige the role of NO in various smooth muscles where NO is a mediator. The present study was undertaken to compare the physiological responses of the rat gastric smooth muscle in response to NANC nerve stimulation and to PIANO. Photolysis of L-NAME, D-NAME and streptozotocin (572) by UV light in the bathing medium caused relaxation of rat gastric fungus that contracted with carbachol, but was resistant to tetrodotoxin (TTX, 1 $\mu$M). Electrical stimulation (20 V, 2~32 Hz, 0.2 msec, 10s) of the gastric fundus, in the presence of atropine and guanethidine, induced frequency-dependent, TTX-sensitive relaxation. Sodium nitroprusside (1 nM-10 $\mu$M), a NO donor, mimicked the relaxations observed after NANC-stimulation or PIANO. Furthermore, PIANO caused UV light exposure time-dependent increase of CGMP in rat gastric fungus strips. These results provide another evidence indirectly that NO is one of the mediators of the NANC inhibitory nerve stimulation in the rat gastric fundus.

• The Korean Journal of Physiology and Pharmacology
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• 제2권1호
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• pp.63-68
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• 1998

Nitric oxide (NO)-mediated relaxation in vascular smooth muscle involves not only activation of guanylate cyclase but also hyperpolarization of the membrane. It has been shown that depolarization decreases the [$Ca^{2+}$] sensitivity of myosin light chain kinase in arterial smooth muscle, and nitric oxide (NO)-mediated relaxation was attenuated in this situation. However, why potassium inhibits or attenuates the action of EDRF/NO is not clear. Therefore, we investigated the magnitude of relaxation and cGMP contents using measures known to release NO, such as photorelaxation, photo activated NO-mediated relaxation, and NO-donor (SNP)-mediated relaxation in porcine coronary arterial rings in which contractile conditions were made by different degree of depolarization, i.e., contraction in response to U46619 or U46619 plus KCl. In all cases, the magnitude of relaxation was significantly greater (P＜0.05) in U46619-contracted rings than in U46619+KCl-contracted ones. Although accumulation of cGMP was evident with three measures employed in the present study, no difference was found in cGMP contents between U46619 and U46619+KCl conditions, indicating that the diminished relaxation in KCl containing solution is cGMP-independent mechanism(s). To understand this further, cytosolic $Ca^{2+}$ changes due to NO were compared in rat thoracic aorta by exploiting photoactivated NO using streptozotocin (STZ) that was contracted with either NE or KCl. Fura-3 $[Ca]_{cyt}$ signal caused by NO was small and transient in high $K^+$-, but large and sustained in NE-contracted aorta. The inhibitory potency of STZ expressed in terms of $IC_{50}$ was 5.14 and 3.88 ${\mu}M$ in NE and in high $K^+$, respectively. These results suggest that modification of the cellular mobilization of $Ca^{2+}$ rather than cGMP levels may be an important mechanism for the NO-mediated relaxation when vascular membrane is depolarized, such as atherosclerosis and hypertension.

• 대한약리학회지
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• 제31권3호
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• pp.279-284
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• 1995

본 연구의 목적은 외부에서 nitric oxide (NO)를 투여 하였을때 심근 수축력, 심박동수의 변화 및 혈관 평활근에 대한 효과를 비교함으로서 NO에 대한 이들 장기의 민감도가 서로 같은지 또는 상이한지를 알아보고자 하였다. 본 실험에서는 PIANO 방법에 의한 근장력의 변화와 아울러 심근에서의 $Ca^{2+}$ current를 측정하였다. 랫트의 심방근에 대한 PIANO $(STZ,\;100\;{\mu}M)$는 심근수축력 및 심박동수에 전혀 변화를 주지 않았지만 혈관 평활근에서는 강한 이완 작용을 나타내었다. 한편, 8-Br-cGMP도 고농도 $(100\;{\mu}M)$에서만 심근 수축력을 억제하였다. 토끼의 심방근세포에서 Whole cell voltage patch clamp를 사용시 bradykinin, SNP, 8-Br-cGMP 및 PIANO는 $Ca^{2+}$ current를 억제하였다. 이러한 사실은 외부에서 공급되는 NO에 대한 심근과 혈관 평활근의 반응에는 민감도의 차이가 있음을 암시하며 더 나아가 심근의 경우에도 NO 반응에는 종 (species)간의 차이와 동일 종이라 하더라도 세포(cell)와 장기(tissue)에 차이가 있을 가능성을 제시하였다.

• 대한약리학회지
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• 제30권3호
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• pp.331-336
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• 1994

본 연구의 목적은 광 유도에 의한 nitric oxide (PIANO)유리가 혈관이완에 대해 cyclic GMP (cGMP)가 관여하는 지의 여부와 아울러 ${\alpha}$-수용체를 통한 수축에 PIANO가 어떻게 작용하는 지를 파악하고자 하였다. In vitro 실험에서 흰쥐의 대동맥을 준 최고농도의 phenylephrine (PE)으로 수축시킨 후 nitric oxide 생성을 변화시키는 약물이나 광민감성 (photosensitizing) 약물에 대한 반응을 등장력 변화로 기록하였다. PIANO에 의한 혈관이완은 광노출 강도와 기간 및 광민감성 약물농도에 비례하여 증가하였고 cGMP의 증가를 수반하였다. PE에 의해 증대되는 phosphatidylinositide(PI) 전환은 PIANO에 의해 억제되었다. 이상의 결과는 cGMP의 증가로 인해 PIANO에 의한 혈관이완이 일어나며 ${\alpha}$-아드레날성 수용체 자극에 의한 PI 전환의 억제현상은 cGMP 증가의 결과로 생각할 수 있다. 결론적으로 PIANO에 의한 혈관이완은 cGMP의 증가로 인함을 확인할 수 있었다.