The relaxation effect of endocannabinoid anandamide on isolated rat bladder and vas deferens tissues and possible mechanisms.

BACKGROUND: The endocannabinoid system plays important roles in various systems, including the genitourinary system; however, its mechanism of action is not fully understood. OBJECTIVES: This study aimed to investigate the direct relaxant effects of anandamide and its possible mechanisms in isolated rat bladder and vas deferens tissues. METHODS: Twenty-one adult male Wistar albino rats were used. Bladder and vas deferens (prostatic and epididymal portions) tissues were mounted in 10 mL of organ baths. Relaxation responses to anandamide were recorded at 3 and 10 µM concentrations. After the rest period, the procedures were repeated in the presence of cannabinoid (CB) and vanilloid receptor antagonists, various potassium channel blockers, cyclo-oxygenase, and nitric oxide synthase inhibitors. In different tissues to investigate the Ca2+-channel antagonistic effect of anandamide, concentration-response curves to CaCl2 were obtained in the absence and presence of anandamide. RESULTS: Anandamide caused a significant relaxation response in the bladder and epididymal vas deferens tissues, but not in the prostatic portion. The effect of anandamide was antagonized in the presence of the CB1 antagonist AM251 or the non-selective potassium channel blocker tetraethylammonium in bladder tissue. In the epididymal vas deferens, anandamide significantly inhibited the calcium contraction responses, especially at high concentrations. The CB2 antagonist AM630 reversed this inhibition. CONCLUSIONS: The results show that anandamide has a direct relaxant effect on the isolated rat bladder and epididymal vas deferens. Anandamide triggers different mechanisms in different types of tissues, and further studies are needed to elucidate the mechanism of action of anandamide.

Effects of taurine on vascular tone.

Taurine is widely distributed at high concentrations in mammalian tissues, and it plays an important role in a wide range of biological effects including modulation of cardiovascular functions. This review summarizes the role of taurine in vascular tone and blood pressure modulation based on experimental and human studies. It is well established that supplementation of taurine prevents development of hypertension in several animal models and p.o. taurine administration reduces blood pressure in hypertensive patients. Both central and peripheral actions of taurine may be involved in its hypotensive effects. In isolated animal arteries, taurine exerts vasodilation through endothelium-dependent and independent mechanisms. Several studies showed that taurine relaxed various animal arteries through opening potassium channels. We have recently shown that taurine relaxes human internal mammary and radial arteries by opening large conductance Ca2+-activated K+ channels. To date, the molecular mechanism(s) involved in the vascular effects of taurine are largely unknown and require further investigation. Clarifying the mechanisms in which taurine affects the vascular system may facilitate the development of therapeutic and/or diet-based strategies to reduce the burden of vascular diseases.

Propofol Relaxes Isolated Rat Aorta through BKCa Activation.

BACKGROUND: Propofol is an intravenous anesthetic that can be used for the induction and maintenance of anesthesia. In the present study, it was aimed to investigate the mechanism of vasodilator action of propofol in the rat aorta (RA). METHODS: The RA rings were suspended in isolated organ baths and tension was recorded isometrically. First, potassium chloride (KCl) and phenylephrine (PE) were added to organ baths to form precontraction. When the precontractions were stable, propofol (1, 10, and 100 µM) was added cumulatively to the baths. The antagonistic effect of propofol on KCl (45 mM), PE (1 µM), 5-hydroxytryptamine (5-HT) (30 µM), and calcium chloride (CaCl2) (10 µM to 10 mM) induced contractions in the vascular rings were investigated. Propofol-induced relaxations were also tested in the presence of the K+ channel inhibitors tetraethylammonium (TEA, 1 mM), glibenclamide (GLI, 10 µM), 4-aminopyridine (4-AP, 1 mM), and barium chloride (BaCl2, 30 µM). RESULTS: Preincubation with propofol (1, 10, and 100 µM) did not affect the basal tone but inhibited the contraction induced by KCl, PE, 5-HT, and CaCl2-induced contractions. Propofol-induced relaxation was not effected by 4-AP, GLI, and BaCl2. However, TEA inhibited propofol-induced relaxations significantly. CONCLUSIONS: The propofol induces relaxation in contracted RA and inhibits KCl, PE, 5-HT, and CaCl2-induced contractions. The results demonstrate that the mechanism of action of propofol-induced vasodilation in the RA may be related to large conductance Ca2+-activated K+ channel activation.

Potassium channels in vascular smooth muscle: a pathophysiological and pharmacological perspective.

Potassium (K+ ) ion channel activity is an important determinant of vascular tone by regulating cell membrane potential (MP). Activation of K+ channels leads to membrane hyperpolarization and subsequently vasodilatation, while inhibition of the channels causes membrane depolarization and then vasoconstriction. So far five distinct types of K+ channels have been identified in vascular smooth muscle cells (VSMCs): Ca+2 -activated K+ channels (BKC a ), voltage-dependent K+ channels (KV ), ATP-sensitive K+ channels (KATP ), inward rectifier K+ channels (Kir ), and tandem two-pore K+ channels (K2 P). The activity and expression of vascular K+ channels are changed during major vascular diseases such as hypertension, pulmonary hypertension, hypercholesterolemia, atherosclerosis, and diabetes mellitus. The defective function of K+ channels is commonly associated with impaired vascular responses and is likely to become as a result of changes in K+ channels during vascular diseases. Increased K+ channel function and expression may also help to compensate for increased abnormal vascular tone. There are many pharmacological and genotypic studies which were carried out on the subtypes of K+ channels expressed in variable amounts in different vascular beds. Modulation of K+ channel activity by molecular approaches and selective drug development may be a novel treatment modality for vascular dysfunction in the future. This review presents the basic properties, physiological functions, pathophysiological, and pharmacological roles of the five major classes of K+ channels that have been determined in VSMCs.

Dental resin curing blue light induces vasoconstriction through release of hydrogen peroxide.

Dental resin curing blue light (BL) is frequently used during treatments in dental clinics. However, little is known about the influence of BL irradiation on pulpal blood vessels. The aim of the present study was to investigate the mechanism of effect of BL irradiation on vascular tone. Rat aorta (RA) rings were irradiated with a BL source in organ baths, and the responses were recorded isometrically. Effect of BL irradiation on phenylephrine (PE) -precontraction and acetylcholine (ACh) -induced relaxation after PE -precontraction were obtained and compared in BL -irradiated and control RA rings. Effect of 20 min preincubation with catalase (enzyme that breaks down hydrogene peroxide, 1200 u/ml) on PE -precontraced and BL-irradiated rings was also evaluated. Total oxidative stress (TOS) and total antioxidant capacity (TAC) in BL-irradiated and control RA preparations were measured with special assay kits and spectrophotometry. BL slightly decreased ACh -induced endothelium -dependent relaxations in PE (1 µM) -precontracted RA rings (n = 6, p > 0.05 vs. control). BL induced marked contraction 23.88 + 3.10% of PE (maximum contraction) in isolated RA ring segments precontracted with PE (p < 0.05 vs. control). The contractile effect of BL was inhibited by 1200 u/ml catalase (n = 6, p < 0.05 vs. control). BL irradiation increased the level of TOS in RA rings (n = 6, p < 0.05 vs. control). TAC levels were similar in BL-irradiated and control preparations. These results suggest that BL induces contraction in RA, and the mechanism of this effect may to be through release of hydrogen peroxide.

Taurine relaxes human radial artery through potassium channel opening action.

The vascular actions and mechanisms of taurine were investigated in the isolated human radial artery (RA). RA rings were suspended in isolated organ baths and tension was recorded isometrically. First, a precontraction was achieved by adding potassium chloride (KCl, 45 mM) or serotonin (5-hydroxytryptamine, 5-HT, 30 µM) to organ baths. When the precontractions were stable, taurine (20, 40, 80 mM) was added cumulatively. Antagonistic effect of taurine on calcium chloride (10 µM to 10 mM)-induced contractions was investigated. Taurine-induced relaxations were also tested in the presence of the K+ channel inhibitors tetraethylammonium (1 mM), glibenclamide (10 µM) and 4-aminopyridine (1 mM). Taurine did not affect the basal tone but inhibited the contraction induced by 5-HT and KCl. Calcium chloride-induced contractions were significantly inhibited in the presence of taurine (20, 40, 80 mM) (p<0.05). The relaxation to taurine was inhibited by tetraethylammonium (p<0.05). However, glibenclamide and 4-aminopyridine did not affect taurine-induced relaxations. Present experiments show that taurine inhibits 5-HT and KCl-induced contractions in RA, and suggest that large conductance Ca2+-activated K+ channels may be involved in taurine-induced relaxation of RA.

The histopathological and pharmacodynamic effects of intradetrusor decorin injected in a rabbit partial bladder outlet obstruction model.

PURPOSE: To evaluate whether or not the bladder function can be protected by supporting the detrusor with decorin levels during the fibrotic process. METHODS: Forty-two male rabbits were divided into three main groups, partial bladder outlet obstruction (pBOO) group, pBOO + intradetrusor decorin-injected (IDI) group and control group. Both pBOO and pBOO + IDI groups were divided into three subgroups according to the killing schedule. Histopathological, immunohistochemical and pharmacodynamics studies were performed for the evaluation of fibrotic process and tissue characteristics. RESULTS: Histopathological evaluation revealed statistically significant high fibrosis levels for both pBOO and pBOO + IDI groups when compared with control. Strikingly the antifibrotic effect of decorin was significant on 2nd, 4th and 8th week and increased as time passed. Immunohistochemical analysis was revealed high expressions of anti-TGF-ß1 and decorin levels in all pBOO + IDI groups. Pharmacodynamical results were also revealed better contraction responses in favor of 2nd, 4th and 8th week groups of pBOO + IDI groups, when compared with pBOO groups. In addition, the contraction responses against the depolarizer agent KCl were increased in the three decorin-administrated groups. CONCLUSION: Our study demonstrates the antifibrotic effects of decorin on bladder fibrosis. Strikingly, this antifibrotic effect is shown in histopathological, immunohistochemical and pharmacodynamics studies. Although further studies are warranted to make more decisive inferences regarding its clinical use, our study has the proper pride to be the first step of this time course.