Yusuf Sarioglu

Vasorelaxing properties of some phenylacridine type potassium channel openers in isolated rabbit thoracic arteries.

In this study, 12 new 2,2,7,7-tetramethyl-9-aryl-2,3,4,5,6,7,9,10-octahydro-1,8-acridindione derivatives were synthesised and their effects on vascular potassium channels and mechanism of induced relaxations on phenylephrine-induced contractile responses in isolated rabbit thoracic arteries was investigated. Pinacidil was used as standard potassium channel openers in this study. Compounds 1-12 and pinacidil exerted concentration-dependent relaxation responses precontracted phenylephrine in the aortic rings with the efficacy order: 11>pinacidil>7>2>8>3>1>4>10>6>9>5>12.

Reactive oxygen species mediate abnormal contractile response to sympathetic nerve stimulation and noradrenaline in the vas deferens of chronically diabetic rats: effects of in vivo treatment with antioxidants.

Previous studies suggest that a link exists between increased oxidative stress and diabetic neuropathy. Moreover, antioxidants may protect neurones from the degenerative effects of reactive oxygen species. In our study, we used streptozotocin (STZ)‐diabetic rats in a 8‐month chronic diabetes model to study the effects of in vivo treatment with stobadine (ST), a pyridoindole antioxidant, and vitamin E. STZ‐diabetic rats were treated with ST (24.7 mg/kg/day), vitamin E (d,l‐alpha‐tocopheryl acetate, 400–500 IU/kg/day) or ST plus vitamin E through an intra‐oral catheter for a 8‐month period beginning 10 days after STZ injection. Blood glucose and HbA1c levels were increased in diabetic rats by about 400 and 100%, respectively. Antioxidant treatment significantly decreased haemoglobin glycosylation (P < 0.05). We also determined the effects of chronic diabetes on sympathetic neurotransmission by measuring the contractility of isolated vas deferens. Furthermore, we investigated contractions elicited by electrical field stimulation (EFS) (1–64 Hz) which were significantly decreased in diabetic rats when compared with control rats. Treatment with ST or vitamin E alone partly enhanced the amplitude of the contractions induced by EFS, but a combination of ST and vitamin E treatment showed no additional effects. Contractile response of the vas deferens to exogenous noradrenaline, was increased in diabetic rats when compared with control rats. While the addition of vitamin E alone had no effect, ST completely returned noradrenaline‐induced contractions to basal levels. The tension induced by 120 mm KCl was not statistically different among the experimental groups. In normal rats, EFS‐induced contractions were significantly inhibited by pyrogallol (10−4 m), a free‐radical generator. Percentage inhibition of pyrogallol on EFS (32 Hz)‐induced contractions in ring sections was 48 ± 5.8 in control, 75 ± 5.5 in untreated‐diabetic, 54 ± 2.7 in ST‐treated diabetic, and 58 ± 4.7 in vitamin E‐treated diabetic rats. Combining both ST and vitamin E treatment had the same effects as each antioxidant alone with a percent inhibition of 48 ± 6.8. These results are consistent with the degenerative changes seen in sympathetic nerves and the abnormal function observed in chronically diabetic rats, leading to a decrease in EFS response and an increase in response to adrenergic agonists in the vas deferens. Furthermore, we demonstrated that reactive oxygen species are responsible for impaired sympathetic neurotransmission and abnormal function of diabetic vas deferens, and that a combination of antioxidants may be better for the therapy of reproductive system disabilities in male diabetics.

Effects of experimental obstructive jaundice on contractile responses of dog isolated blood vessels: role of endothelium and duration of bile duct ligation.

1. We examined the effects of experimental obstructive jaundice caused by bile duct ligation (BDL) on vascular smooth muscle function, as well as the underlying mechanisms involved, by recording responses to noradrenaline (NA), 5‐hydroxytryptamine (5‐HT) and acetylcholine (ACh) in canine isolated renal arteries and to NA in isolated mesenteric arteries in vitro. All studies were performed 7 days after the onset of BDL in renal arteries and 3, 7 and 15 days after the onset of BDL in mesenteric arteries.

Corporal reactivity to adenosine and prostaglandin E1 in alloxan-induced diabetic rabbit corpus cavernosum, and the effect of insulin therapy.

To investigate the changes in corporal reactivity to adenosine and prostaglandin E1 (PGE1 ) in corpus cavernosal strips from alloxan‐induced diabetic rabbits and to determine the effects of insulin therapy.

The role of K(+) channels on the inhibitor effect of sevoflurane in pregnant rat myometrium.

UNLABELLED Volatile anesthetics and K(+) channel openers inhibit spontaneous contractions in myometrial smooth muscle. Volatile anesthetics modulate K(+) channel activity. We investigated the role of two K(+) channel blockers on the effect of sevoflurane in pregnant rat myometrium. Term pregnant rat uteri were excised, and cross-sectional myometrial strips were mounted for isometric force recording. Sevoflurane inhibited the amplitude and frequency of spontaneous myometrial contractions in a concentration-dependent manner. The maximal inhibition measured in amplitude and frequency of spontaneous myometrial contractions with sevoflurane (at 3 minimum alveolar anesthetic concentration) was 44.32% and 33.32% of control contractions, respectively. Tetraethylammonium (TEA) and glibenclamide, K(+) channel blockers, increased spontaneous myometrial contractions in a concentration-dependent manner. Sevoflurane responses were repeated at concentrations with no effect on spontaneous contractility of TEA, a Ca(2+)-activated K(+) channel blocker, and glibenclamide, an adenosine triphosphate-sensitive K(+) channel blocker, in myometrial strips. TEA (3.10(-4) M) caused a significant reduction in sevoflurane-induced inhibitor responses, but glibenclamide (10(-6) M) did not. Sevoflurane-induced maximal inhibition (at 3 minimum alveolar anesthetic concentration) on amplitude and frequency of spontaneous myometrial contractions in the presence of TEA (3.10(-4) M) was 31.85% and 22.33% of control contractions, respectively (P < 0.05). These results suggest that the in vitroapplication of sevoflurane inhibited the amplitude and frequency of spontaneous myometrial contractions in pregnant rats in a concentration-dependent manner. Such inhibition was reduced by TEA. The inhibition of myometrial smooth muscle induced by sevoflurane seems to be mediated, at least in part, via activation of Ca(2+)-activated K(+) channels, because inhibition was reduced by TEA. IMPLICATIONS In this study, we found that sevoflurane causes significantly decreased myometrial contractile activity in pregnant rats. The inhibition of myometrial smooth muscle induced by sevoflurane seems to be mediated, at least in part, via activation of Ca(2+)-activated K(+) channels, because inhibition was reduced by tetraethylammonium.

Impaired Contraction and Relaxation in the Aorta of Streptozotocin-Diabetic Rats

It is known that diabetes mellitus alters the vascular responsiveness to several vasoconstrictors and vasodilators. Endothelium-derived nitric oxide is a potent endogenous nitrovasodilator, and endothelin-1 (ET-1) is a potent endothelium-derived vasoconstrictor substance. They play a major role in the modulation of vascular tone. Selective impairment of endothelium-dependent relaxation and impaired vasoconstriction in response to ET-1 could result in vascular disorders. The purpose of our study was to determine whether vascular responses to ET-1 and endothelium-dependent relaxing substances are impaired in rats with streptozotocin-induced diabetes of 2 weeks duration. Endothelium-dependent relaxations produced by carbachol and ATP in aortic rings precontracted with phenylephrine were significantly attenuated in rings from diabetic rats, but the endothelium-independent relaxations produced by sodium nitroprusside and adenosine in diabetic preparations were not changed when compared to the corresponding controls. The ET-1-induced contractions were significantly attenuated with no change in agonist potency (pD2 value) in aortae with and without endothelium obtained from diabetic rats when compared to those from controls. Mechanical removal of the endothelium did not significantly change ET-1 responses of aortae from either diabetic or control rats compared with responses of aortae with intact endothelium. These results suggest that, in this diabetic model, the contractile responsiveness of thoracic aortic muscles and the endothelial functions are significantly altered during 2 weeks of diabetes.

Relaxant effect of omeprazole and lansoprazole in guinea pig gallbladder muscle strips in vitro

Background. The aim of this study was to investigate the role of omeprazole and lansoprazole, H+-K+ ATPase inhibitors, in gallbladder smooth muscle contractility in vitro. Methods. Gallbladder muscle strips obtained from guinea pigs were mounted in an organ bath. The responses of both precontracted strips and strips under basal tension to omeprazole and lansoprazole were determined. Results. Spontaneous contractile activity was blocked following omeprazole and lansoprazole administration. The agents also caused concentration-dependent relaxation in carbachol- and KCl-precontracted gallbladder muscle strips. Pretreatment with atropine (1 µM), NW-nitro l-arginine methyl ester (l-NAME; 30 µM), indomethacin (10 µM), ammonium chloride (7.5 mM), sodium acetate (7.5 mM), tetraethylammonium chloride (0.5 mM), glibenclamide (1 µM), 4-aminopyridine (0.1 mM), or clotrimazole did not inhibit this relaxation. Gallbladder strips were placed in high-concentrtion potassium (80 mM), calcium-free solution. The contraction produced with the addition of Ca2+ (2.5 mM) was completely relaxed by omeprazole, lansoprazole, and nifedipine separately. Conclusions. These results demonstrate that omeprazole and lansoprazole have potent inhibitory effects on spontaneous contractions and cause dose-dependent relaxation in precontracted gallbladder smooth muscle strips of guinea pig in vitro. This effect could be due to blockade of the calcium channels.

Evidence of relaxant effect of omeprazole in rabbit corpus cavernosum in vitro

The present experiments were designed to investigate the effects of omeprazole, a H(+)-K+ ATPase inhibitor, on corporal smooth muscle tone in vitro. All spontaneous contractile activity in the corpus cavernosum was blocked following omeprazole (0.1 mM-1 mM) administration. However atropine (1 microM), Nw-nitro L-arginine methyl ester (L-NAME, 30 microM) or indomethacin (10 microM) did not affect the spontaneous contraction. Omeprazole (10 microM-1 mM) concentration-dependently induced relaxation in corporal smooth muscle precontracted with 10 microM phenylephrine or 80 mM KCl. Pretreatment of corporal tissue with L-NAME (30 microM), indomethacin (10 microM), ammonium chloride (7.5 mM), sodium acetate (7.5 mM), tetraethyl ammonium chloride (0.5 mM) or glibenclamide (1 microM) had no effect on the omeprazole induced relaxant responses. Nimodipine, an L-type Ca++ channel blocker, relaxed corporal strips precontracted with 80 mM KCl. Collectively, these results indicate that the inhibition of spontaneous contraction and the relaxation of precontracted corporal smooth muscle by omeprazole is probably mediated by the blockade of calcium channels. Further work is needed to determine the cellular mechanism(s) of action by which omeprazole acts on corpus cavernosum smooth muscle.

Inhibitor effect of omeprazole in isolated human myometrial smooth muscle

The aim of the present study was to investigate the effect of omeprazole, an H+-K+-ATPase inhibitor, in myometrial smooth muscle strips from women undergoing elective caesarean section at term. Isolated myometrial strips taken with informed consent were obtained from eight pregnant women undergoing elective caesarean section at term (not in labour) and mounted in organ baths for recording of isometric tension. We recorded the effect of increasing concentrations of omeprazole on spontaneous and Ca2+-induced contractions of myometrial smooth muscle and on contractions of myometrial smooth muscle pretreated with indomethacin (3 x 10(-6) M) and L-NAME (3 x 10(-5) M). Omeprazole (10(-4)-10(-3) M) decreased the amplitude and frequency of spontaneous contractions in a time- and concentration-dependent manner in all myometrial smooth muscle isolated from pregnant women. The decrease in amplitude of contractions in myometrial smooth muscle reached statistical significance beginning from the concentration of 3 x 10(-4) M. Addition of indomethacin (3 x 10(-6) M) and L-NAME (3 x 10(-5) M) in to the organ baths 30 min before did not change relaxation responses to omeprazole. When 8 mM Ca2+-precontracted in Ca2+-free medium myometrial smooth muscle were exposed to increasing concentrations of omeprazole (10(-5)-10(-3) M), omeprazole produced relaxation responses in a time- and concentration-dependent manner, reaching statistical significance at 10(-4) M. These results show: (1) omeprazole time- and concentration-dependently decreased spontaneous contractile activity in myometrial smooth muscle isolated from pregnant women, (2) omeprazole-induced relaxations was not influenced by indomethacin and N(G)-nitro-L-arginine methyl ester (L-NAME), suggesting that it is not mediated by cyclooxygenase products and nitric oxide, and (3) omeprazole brought about time- and concentration-dependently relaxation of myometrial smooth muscle precontracted by 8 mM Ca2+ in Ca2+-free medium. This effect of omeprazole may be due to blockade of the calcium channels.

The evaluation of the effects of renal failure on erectile dysfunction in a rabbit model of chronic renal failure.

To determine whether chronic renal failure (CRF) reduces nitrergic relaxant responses in a rabbit model.