Comparison of In Vitro Effects of Opioid Analgesics on Spontaneous Proximal and Distal Colon Contractions in Healthy Rats and Rats with Peritonitis.

OBJECTIVE: The goal of this study was to investigate and compare the effects of opioids on proximal and distal colon contractions in normal rats and rats with peritonitis, with and without the presence of naloxone in the environment. METHODS: The study was approved by Cumhuriyet University Ethics committee. In this study, 16 Wistar Albino male rats were used. Rats were divided into two groups. Peritonitis was induced using a cecum ligation and perforation method, 24 h before the tissues of rats in the peritonitis group were collected, and sham surgery was performed 24 h before the tissues of rats in the control group were collected. Twenty-four hours after the surgery, rats' organs were harvested and hung in organ baths. Concentration-dependent inhibitory effects of morphine and meperidine on spontaneous intestinal movements were observed. Any differences between the groups were tested using the Kruskal-Wallis test, and any differences between the groups were tested using the Tukey test. RESULTS: No significant difference was observed between the proximal and distal colon smooth muscle contraction responses in both groups after 80 mM Potassium Chloride (KCl) injection (p>0.005). In the peritonitis group, amplitudes and frequencies of spontaneous contractions in proximal and distal colon significantly increased (p<0.05). Drugs decreased the amplitude and frequency responses in the control group (p<0.05). In the peritonitis group, whereas morphine decreased the amplitude and frequency responses in comparison with the control group (p<0.05), meperidine did not cause any significant changes (p>0.05). In both groups, adding naloxone to the organ baths before adding opioids completely blocked the morphine's inhibitory effect on the amplitude and frequency (p<0.05), but it could not completely block the inhibition caused by meperidine. CONCLUSION: Morphine and meperidine exhibit an inhibitory effect on the intestinal motility in both groups. This effect can be blocked by naloxone completely in morphine, and partially in meperidine.

Investigation of the vasorelaxant effects of moxonidine and its relaxation mechanism on the human radial artery when used as a coronary bypass graft.

OBJECTIVES: In both low- and high-risk patients undergoing coronary artery bypass grafting, the internal mammary artery is the first choice of arterial graft, and the second choice is the radial artery (RA). Unfortunately, RA spasms are a significant problem for a surgical team to overcome in the perioperative and postoperative period. In current surgical practice, the use of vasodilator agents perioperatively in the pending graft preparation is generally accepted and these may be implemented topically, endoluminally or both ways. Moxonidine is the latest second-generation, centrally acting antihypertensive agent, and the intention in this paper is to investigate its direct vasorelaxant effects and relaxation mechanisms on the human radial artery in vitro. METHODS: RA rings were mounted in an organ bath and tested for changes in isometric tension in its relaxation response to moxonidine in the presence and absence of NG-nitro-L-arginine methyl ester (L-NAME, non-specific inhibitor of nitric oxide synthase), idazoxan (non-selective I1 and α2-antagonist) and yohimbine (selective α2-antagonist). RESULTS: Moxonidine induced concentration-dependent relaxations on the RA rings precontracted with phenylephrine (P < 0.05). L-NAME and idazoxan significantly reduced the relaxation caused by moxonidine (P < 0.05), while yohimbine significantly increased the relaxation by moxonidine (P < 0.05). In the presence of L-NAME + idazoxan, the relaxation by moxonidine was eliminated completely (P < 0.05). CONCLUSIONS: We speculate that the relaxant effect of moxonidine may be attributed partly to the synthesis and/or release of nitric oxide, and partly to the stimulation of imidazoline I1 receptors. We suggest that moxonidine may help to prevent RA spasms during the preparation period in operation when used topically or/and endoluminally.

Labetalol, nebivolol, and propranolol relax human radial artery used as coronary bypass graft.

OBJECTIVE: Beta-blockers are a heterogeneous class of agents that are used in the treatment of many cardiovascular diseases, especially hypertension and atherosclerosis, and that are commonly prescribed after cardiac surgery. In the present study, the aim is to investigate the vasorelaxant effects of some common beta-adrenoceptor blockers on the human radial artery in vitro, as well as their relaxation mechanisms. METHODS: Radial artery rings sourced from human patients were mounted in an organ bath and tested for changes in isometric tension in relaxation response to labetalol, nebivolol, and propranolol in the presence and absence of NG-nitro-L-arginine methyl ester (3 × 10(-5) mol/L) and tetraethyl ammonium (3 × 10(-4) mol/L). RESULTS: The labetalol (10(-8) to 10(-4) mol/L), nebivolol (10(-8) to 10(-4) mol/L), and propranolol (10(-8) to 10(-4) mol/L) induced concentration-dependent relaxations on the radial artery rings, which had been precontracted with phenylephrine (10(-6) mol/L). The relaxation response induced by labetalol in the isolated radial artery rings was significantly higher when compared with the nebivolol and propranolol samples (P < .05). NG-nitro-L-arginine methyl ester significantly reduced the relaxation of nebivolol (P < .05), and tetraethyl ammonium significantly reduced the relaxation of labetalol, nebivolol, and propranolol (P < .05). CONCLUSIONS: We speculated that the relaxant effect of labetalol, nebivolol, and propranolol was due partly to the Ca(2+)-activated K(+) channels. In addition, the relaxation induced by nebivolol was largely related with nitric oxide release. Nebivolol, and partly propranolol, may provide significant therapeutic benefit, but labetalol can be a good alternative for coronary artery bypass grafting with radial artery use.

Effects and selectivity of CL 316243, beta-3-adrenoceptor agonist, in term-pregnant rat myometrium.

BACKGROUND/AIMS: Recent evidence supports a predominant role of ß(3)-adrenoceptors at the end of pregnancy in myometrium. This study was designed to characterize the pharmacology of the selective ß(3)-adrenoceptor agonist CL 316243 on oxytocin-induced myometrial contractions and the levels of cAMP and cGMP of myometrial strips isolated from term-pregnant rats. METHODS: Myometrial strips were obtained from term-pregnant Wistar albino rats (n = 10), mounted in organ baths and tested for changes in isometric tension in response to CL 316243 (10(-10)-10(-5) M) on oxytocin-induced myometrial contractions. Effects of CL 316243 on cAMP and cGMP levels in isolated myometrial strips (n = 8) were evaluated by radioimmunoassay kits. We evaluated the effect of increasing concentrations of CL 316243 on myometrial contractions and on contractions of myometrial smooth muscle pretreated with metoprolol, ICI 118.551 and SR 59230A (ß(1)-, ß(2)-, ß(3)-adrenoceptor antagonists, respectively, 10(-6) M). RESULTS: The inhibition of the amplitude of oxytocin-induced contractions by CL 316243 were antagonized with SR 59230A (10(-6) M), but they were not changed by metoprolol (10(-6) M) or ICI 118.551 (10(-6) M). CL 316243 increased cAMP levels compared to the control group. CL 316243 increased cGMP levels, in the CL 316243 group more than in the control group, but this increase is less significant than cAMP levels. CONCLUSION: These results demonstrate that the inhibition of rat myometrial contractions with CL 316243 is mediated by ß(3)-adrenoceptor subtype and increased cAMP and cGMP levels.

Investigation of the cardiac effects of pancuronium, rocuronium, vecuronium, and mivacurium on the isolated rat atrium.

BACKGROUND: Pancuronium, vecuronium, rocuronium, and mivacurium are nondepolarizing neuromuscular blocking agents that affect the cardiovascular system with different potencies. Their cardiovascular effects are clinically significant in the anesthetic management of patients, particularly those undergoing cardiac surgery. OBJECTIVE: We aimed to compare the cardiac effects of these compounds, such as heart rate and developed force, in one species under identical experimental conditions in isolated rat atria. METHODS: The left or right atria of rats were removed and suspended in organ baths. Pancuronium, vecuronium, rocuronium, or mivacurium were added cumulatively (10(-9)-10(-5) M) in the presence and absence of the nonselective ß-blocker propranolol (10(-8) M) and the noradrenaline reuptake inhibitor desipramine (10(-7) M), and heart rate changes were recorded in spontaneously beating right atria. Left atrial preparations were stimulated by electrical field stimulation using a bipolar platinum electrode, and the effects of cumulative concentrations of these nondepolarizing neuromuscular blocking agents on the developed force in the presence and absence of propranolol (10(-8) M) and desipramine (10(-7) M) were recorded. RESULTS: Pancuronium increased heart rate in a dose-dependent manner compared with the control group (P < 0.027). Vecuronium, rocuronium, and mivacurium also increased heart rate in a dose-dependent manner, but the changes were not statistically significant. Although propranolol decreased the pancuronium heart rate effect (P < 0.05), it did not change the heart rate effects with vecuronium, rocuronium, or mivacurium. Desipramine did not change the heart rate effects of vecuronium, rocuronium, mivacurium, or pancuronium. All 4 drugs increased developed force in a dose-dependent manner; the increases were significant at 10(-5) M concentration for pancuronium and at 10(-6) and 10(-5) M concentrations for vecuronium, rocuronium, and mivacurium (P < 0.038). These increases in developed force were abolished with the addition of propranolol. Desipramine did not change the developed force effects of any of the 4 drugs. CONCLUSIONS: The heart rate effect of pancuronium and developed force effects of pancuronium, vecuronium, rocuronium, and mivacurium may occur via direct stimulation of ß receptors. Although our investigation was an in vitro study, the effects found may be important especially under pathologic conditions, such as hypertension, in which patients usually use ß-blocking agents, which cause ß receptor upregulation.

Evaluation of urinary bladder function after acute spinal cord injury: an experimental study.

OBJECTIVES: The aim of this study was to evaluate the efficacy of early surgical decompression of acute spinal cord injury through the evaluation of urinary bladder function in rabbits. MATERIALS AND METHODS: The study was done with 21 New Zealand male rabbits which were 9 to 12 months in age, and weighed an average of 2438 grams (range 2150 to 3550 g). The animals were assigned into four groups as follows: a control group (n=5), a laminectomy group (n=6), a 15-second compression group (n=5) and a 60-second compression group (n=5). A 60 gram compression force was applied on both compression groups with aneurysm clips. All rabbits were sacrificed seven days postoperatively. Urinary bladder tissues were dissected and in vitro relaxation and contraction tests were performed in organ baths. RESULTS: At the beginning of each experiment, 80 mM KCl was added to the isolated organ bath with no significant difference among all four groups (p>0.05). Carbachol was then added to the organ bath and contraction responses were obtained. Carbachol contraction responses were calculated as the percentage of the 80 mM KCl contraction responses, with compression groups showing significant difference from control and sham-operated groups (p<0.05). Electrical field stimulation responses were obtained for all group preparations at 4, 8, 16, 32 Hz frequencies, and showed significant difference in the 15 and 60-second compression groups (p<0.05). The contractility was assessed using E-max and pD2 values. All groups exhibited same pD2 values. CONCLUSION: The study demonstrated a slightly better outcome for bladder contractility with early decompression. However, there was no significant difference between early and delayed decompression groups.

Rho-kinase inhibitors Y-27632 and fasudil prevent agonist-induced vasospasm in human radial artery.

Radial artery (RA) vasospasm remains a potential cause of early graft failure after coronary artery bypass graft surgery, despite pretreatment with alpha-adrenergic or calcium channel blockers. Our aim was to investigate the mechanism of the vasorelaxant effects of Rho-kinase inhibitors (Y-27632 and fasudil) on the human RA. Segments were obtained from 30 patients undergoing coronary artery bypass graft and were divided into 3-4 mm vascular rings. The rings were stimulated with 10(-5) mol/L phenylephrine (PE) by using the isolated tissue bath technique and were relaxed with 10(-6) mol/L acetylcholine. Relaxation responses were recorded for Y-27632 (10(-9)-10(-4) mol/L), fasudil (10(-9)-10(-4) mol/L), and sodium nitroprusside (SNP) (10(-9)-10(-5) mol/L). Y-27632 and fasudil relaxation responses were repeated in either N(G)-nitro-L-arginine (L-NNA), which is a specific endothelial nitric oxide synthase inhibitor, or 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ), which is a guanylate cyclase inhibitor. SNP relaxation responses were repeated in 10(-8) mol/L Y-27632 and 10(-8) mol/L fasudil. Y-27632 and fasudil caused concentration-dependent vasorelaxation in RA rings precontracted with PE, and maximal relaxation (100%) was recorded at the highest concentration used (10(-4) mol/L). The vasorelaxant effects of Y-27632 and fasudil were significantly reduced in the presence of L-NNA and ODQ, and the pD2 values of Y-27632 and fasudil were not changed. The vasorelaxant effects of SNP were significantly increased in the presence of Y-27632 and fasudil, and the pD(2) values of SNP were not changed. These findings indicate that Y-27632 and fasudil caused concentration-dependent vasorelaxation in the RA rings. Because this effect was decreased in a dose-dependent manner by L-NNA and ODQ, the relaxant effects of Y-27632 and fasudil could be due to stimulation by nitric oxide that is being released. Rho-kinase inhibitors may have an important role in preventing vasospasm in arterial grafts used for coronary artery surgery.

Investigation of acute effects of aflatoxin on rat proximal and distal colon spontaneous contractions.

Aflatoxins are one of the most potent toxic, mutagenic, teratogenic, cancerogenic, and immunosuppresive substances that naturally occurring contaminants of food. There are some studies in various animal species that have reported aflatoxin effects on gastrointestinal systems, but acute effects of aflatoxins have not been clearly investigated. In this study, we aimed to investigate the acute gastrointestinal effects of total aflatoxin on rat isolated proximal and distal colon. Aflatoxin was given cumulatively at 10(-8)-10(-5)M concentrations and the amplitude and frequency of proximal and distal colon contractions were increased significantly. In the presence of atropine sulfate (23.6 nM) and morphine (0.3 microM) the amplitude and frequency of aflatoxin induced spontan contractions in the proximal and distal colon decreased significantly, on the other hand, L-NNA (0.3 microM) increased contractions' amplitude and frequency significantly in the proximal colon but not in the distal colon. In conclusion, aflatoxin may increase the amplitude and frequency of contractions by increasing muscarinic activity or by decreasing NO synthase and/or release in proximal colon and by increasing muscarinic activity in the distal colon. These findings of aflatoxin on isolated rat proximal and distal colon may explain their acute gastrointestinal effects in humans and animals.

Alterations in spontaneous contractions of rat proximal and distal colon after peritonitis.

BACKGROUND/PURPOSE: The aim of this study was to investigate the effect of peritonitis on spontaneous contractions of distal and proximal colon smooth muscle isolated from rats. METHODS: Peritonitis was induced by cecal ligation and puncture in 8 rats. Another group of 8 rats underwent a sham operation and acted as controls. Twenty-four hours after the operation, the rats were killed; and their distal and proximal colon smooth muscle was excised and placed in circular muscle direction in a 10-mL organ bath. Changes in the amplitude and frequency of contractions were analyzed before and after the addition of antagonists. RESULTS: Peritonitis induced the increase in the amplitude and frequency of spontaneous contractions. In both distal and proximal colon of the control group, the amplitude of spontaneous contractions was elevated by N(G)-nitro-L-arginine and tetrodotoxin; but the frequency of spontaneous contractions was significantly elevated only in the presence of N(G)-nitro-L-arginine. In both distal and proximal colon of the peritonitis group, the enhanced amplitude and frequency were significantly decreased and returned to control values in the presence of celecoxib. CONCLUSIONS: Peritonitis induces the increase in the amplitude and frequency of spontaneous contractions of distal and proximal colon, which can be attributed to a loss of inhibitor nitrergic and other neural control or rise of cyclooxygenase-2 levels.

Investigation of the vasorelaxant effects of 3-(5'-hydroxymethyl-2'-furyl)-1-benzyl indazole (YC-1) and diethylamine/nitric oxide (DEA/NO) on the human radial artery used as coronary bypass graft.

The radial artery (RA) is used as a spastic coronary bypass graft. This study was designed to investigate the mechanism of vasorelaxant effects of YC-1 (3-(5'-hydroxymethyl-2'-furyl)-1-benzyl indazole), a nitric oxide (NO)-independent soluble guanylate cyclase (sGC) activator, and DEA/NO (diethylamine/nitric oxide), a NO-nucleophile adduct, on the human RA. RA segments (n = 25) were obtained from coronary artery bypass grafting patients and were divided into 3-4 mm vascular rings. Using the isolated tissue bath technique, the endothelium-independent vasodilatation function was tested in vitro by the addition of cumulative concentrations of YC-1 (10-10 to 3 x 10-7 mol/L) and DEA/NO (10-8 to 3 x 10-5 mol/L) following vasocontraction by phenylephrine in the presence or absence of 10-5 mol/L ODQ (1H-(1,2,4)oxadiazole(4,3-a)quinoxalin-1-one), the selective sGC inhibitor, 10-7 mol/L iberiotoxin, a blocker of Ca2+-activated K+ channels, or 10-5 mol/L ODQ plus 10-7 mol/L iberiotoxin. We also evaluated the effect of YC-1 and DEA/NO on the cGMP levels in vascular rings obtained from human radial artery (n = 6 for each drug). YC-1 (10-10 to 3 x 10-7 mol/L) and DEA/NO (10-8 to 3 x 10-5 mol/L) caused the concentration-dependent vasorelaxation in RA rings precontracted with phenylephrine (10-5 mol/L) (n = 20 for each drug). Pre-incubation of RA rings with ODQ, iberiotoxin, or ODQ plus iberiotoxin significantly inhibited the vasorelaxant effect of YC-1, but the inhibitor effect of ODQ plus iberiotoxin was significantly more than that of ODQ and iberiotoxin alone (p < 0.05). The vasorelaxant effect of DEA/NO almost completely abolished in the presence of ODQ and iberiotoxin plus ODQ, but did not significantly change in the presence of iberiotoxin alone (p > 0.05). The pEC50 value of DEA/NO was significantly lower than those for YC-1 (p < 0.01), with no change Emax values in RA rings. In addition, YC-1-stimulated RA rings showed more elevation in cGMP than that of DEA/NO (p < 0.05). These findings indicate that YC-1 is a more potent relaxant than DEA/NO in the human RA. The relaxant effects of YC-1 could be due to the stimulation of the sGC and Ca2+-sensitive K+channels, whereas the relaxant effects of DEA/NO could be completely due to the stimulation of the sGC. YC-1 and DEA/NO may be effective as vasodilator for the short-term treatment of perioperative spasm of coronary bypass grafts.

Mechanism of relaxation induced by nicotine in normal and ovalbumin-sensitized guinea-pig trachea.

Nicotine is an irritant molecule in the cigarette that contributes airway hyper-reactivity. The aim of this study was to investigate the mechanism of these effects and effects of nicotine on the isolated trachea preparations from control and ovalbumin-sensitized guinea-pigs. Nicotine (3x10(-5) to 3x10(-4) M) produced concentration-dependent relaxation on isolated trachea preparations precontracted by carbachol (10(-6) M) in both groups. We found that the relaxant effect of nicotine decreased in the presence of N(w)-nitro L-arginine methyl ester (L-NAME) (10(-6) M), and hexamethonium (10(-2) M) but not in the presence of alpha-bungarotoxin (10(-3) M), and tetrodotoxin (3.1x10(-6) M) in isolated trachea preparations in both groups. The relaxant effect of nicotine was less significant in isolated trachea preparations from ovalbumin-sensitized guinea-pigs than from control guinea-pigs (P<0.05). The contractions elicited by carbachol (10(-6) M) were not significantly different in the ovalbumin-sensitized group than in the control group. Nicotine (10(-4) M) significantly increased the cGMP levels in trachea preparations compared with the control preparations.(P<0.05). These results suggest that nicotine-induced relaxation response in normal and ovalbumin sensitized guinea-pigs trachea is at least in part mediated by nitric oxide (NO) since it was significantly reduced in the presence of L-NAME. The decreased relaxation response to nicotine in ovalbumin sensitized guinea-pigs trachea may be due to impaired production and/or liberation of NO.

Effects of intravenous anesthetics on the human radial artery used as a coronary artery bypass graft.

OBJECTIVE: Intravenous anesthetics are often used for anesthesia, sedation, and analgesia in the intraoperative and postoperative periods of coronary artery bypass graft (CABG) surgery. This study was designed to investigate the direct effects of intravenous anesthetics on the human radial artery (RA). DESIGN: In vitro, prospective with repeated measures. SETTING: University research laboratory. PARTICIPANTS: RA segments (n = 20) were obtained from CABG surgery patients and were divided into 3- to 4-mm vascular rings. INTERVENTIONS: Using the organ bath technique, the endothelium-independent vasodilatation function was tested in vitro by the addition of cumulative concentrations of thiopental, ketamine, etomidate, and propofol after vasocontraction by phenylephrine in the presence of N(G)-nitro-L-arginine methyl ester (L-NAME) and indomethacin. MEASUREMENTS AND MAIN RESULTS: Thiopental (10(-8) to 10(-4) mol/L), ketamine(10(-8) to 10(-4) mol/L), propofol (10(-8) to 3 x 10(-4) mol/L), and etomidate (10(-8) to 3 x 10(-4) mol/L) caused concentration-dependent vasorelaxation in human RA rings precontracted with phenylephrine in the presence of L-NAME and indomethacin (n = 20, for each drug). The pEC(50) and maximum relaxant effect values of thiopental and ketamine were significantly higher than for etomidate and propofol (p < 0.05). CONCLUSIONS: These findings indicate that thiopental, ketamine, etomidate, and propofol produce concentration-dependent relaxation on RA rings from humans. Thiopental and ketamine are more potent relaxant agents than etomidate and propofol. Intravenous anesthetics may be effective as alternative vasodilators for treatment of intraoperative and postoperative spasm of coronary artery grafts.

Effects of formoterol and BRL 37344 on human umbilical arteries in vitro in normotensive and pre-eclamptic pregnancy.

Alterations in vascular responses to beta-adrenoceptor agonists in normotensive pregnancy and pre-eclampsia are not fully understood. Thus, we studied changes in vasodilator responses to beta(2)-adrenoceptor agonist formoterol and beta(3)-adrenoceptor agonist BRL 37344 on umbilical arteries isolated from normotensive (n=12) and pre-eclamptic (n=12) pregnant women. Changes in the relaxant effect of formoterol and BRL 37344 were investigated by measuring isometric tensions in endothelium-denuded strips of umbilical arteries in the presence or absence of metoprolol, ICI 118.551 and SR 59230A (beta(1), beta(2), beta(3)-adrenoceptor antagonists, respectively, 10(-6) mol/L). Effects of formoterol and BRL 37344 on cAMP levels of umbilical arteries were evaluated by radioimmunoassay kits. Formoterol (10(-10)-10(-4) mol/L) and BRL 37344 (10(-10)-10(-4) mol/L) caused concentration-dependent relaxation of the contraction induced by phenylephrine (10(-5) mol/L) in umbilical artery strips isolated from both groups. E(max) values of formoterol and BRL 37344 (for normotensive pregnant women: 87.33+/-0.87 and 53.25+/-1.17 vs. for pre-eclampsia: 73.68+/-1.58 and 43.64+/-1.19, n=12, P>0.05, respectively) were significantly smaller in strips from pre-eclamptic women (P<0.05), with no significant change in pD(2) values. E(max) values of formoterol were significantly higher than those of BRL 37344 in both tissue (P<0.05). ICI 118.551 and SR 59230A, but not metoprolol, antagonized the relaxant effects of formoterol and of BRL 37344 on umbilical artery strips isolated from normotensive and pre-eclamptic pregnant women. Formoterol and BRL 37344 increased cAMP levels in both groups, but less significant in pre-eclamptic strips (P<0.05). These results suggest that the relaxation caused in human umbilical arteries by formoterol and BRL 37344 is mediated by a mixed population of beta(2)- and beta(3)-adrenoceptor subtypes, with contribution of cAMP. Umbilical arteries from subjects with pre-eclampsia showed a weaker beta(2)- and beta(3)-receptor-mediated relaxation to formoterol and BRL 37344, suggesting that the reduced action of formoterol and BRL 37344 may be partly due to a decreased effect of cAMP.

Do antibiotics contribute to postoperative ileus? Contractile responses of ileum smooth muscle in Guinea pigs to long-term parenteral ceftriaxone and ampicillin.

BACKGROUND: Antibiotics may impair small bowel smooth muscle contractility and contribute to postoperative ileus. The aim of this study was to compare the contractile responses of ileum smooth muscle to different agonists in guinea pigs treated with ceftriaxone (Rocephin; F. Hoffman-La Roche, Kaiseraugst, Switzerland) or ampicillin (Ampisina; Mustafa Nevzat Ilaç Sanayii AS, Istanbul, Turkey). METHODS: Twenty-four adult guinea pigs were randomly divided into three groups. Whereas eight of these received ceftriaxone sodium (100 mg/kg per day, i.m.) for 10 days, another eight guinea pigs received ampicillin (50 mg/kg per day, i.m.) for 10 days and the remaining eight served as the control group receiving 1 mL distilled water during 10 days as placebo. By the end of 10 days, the animals were killed and their ilea were excised. Ileum segments were placed in an organ bath; concentration-response relationship for carbachol and histamine were obtained by adding the reagent cumulatively to the bath. RESULTS: pD(2) values being the same, maximum contractile responses (E(max)) to carbachol and histamine were significantly reduced in the ceftriaxone sodium group compared with the control group. No significant differences in E(max) and pD(2) values to carbachol and histamine were observed between the ampicillin group and the control group. CONCLUSION: These data indicate that whereas ceftriaxone may impair small bowel smooth muscle contractility, ampicillin does not. There are implications for the long-term use of parenteral antibiotics in the postoperative period.

Comparison of effects of formoterol and BRL 37344 on isolated term-pregnant rat myometrial strips in vitro.

This study was designed to compare the effects of beta-adrenoceptor agonists formoterol and BRL 37344 on spontaneous contractions and the levels of cAMP and cGMP of myometrial strips isolated from timed-pregnant rats. Myometrial strips were obtained from term-pregnant Wistar albino rats (n=12), mounted in organ baths and tested for changes in isometric tension in response to formoterol and BRL 37344. We evaluated the effect of increasing concentrations of formoterol and BRL 37344 on oxytocin-induced myometrial contractions and on contractions of myometrial smooth muscle pretreated with metoprolol, ICI 118.551 and SR 59230A (beta1, beta2, beta3-adrenoceptor antagonist, respectively, 10(-6) M). Effects of formoterol and BRL 37344 on cAMP and cGMP levels in isolated myometrial strips (n=6) were evaluated by radioimmunoassay kits. Formoterol (10(-12)-10(-8) M) and BRL 37344 (10(-11)-10(-5) M) concentration-dependently decreased the amplitude of oxytocin-induced contractions. E(max) value (100%) of formoterol was increased significantly more than E(max) value (70.6%) of BRL 37344 (P<0.05), with no change in pD(2) value (9.54+/-0.12 and 9.12+/-0.12, respectively). The inhibition of the amplitude of oxytocin-induced contractions by formoterol was antagonized with ICI 118.551 (10(-6) M), but they were not changed by metoprolol (10(-6) M) or SR 59230A (10(-6) M). The inhibition of the amplitude of oxytocin-induced contractions by BRL 37344 were antagonized with SR 59230A (10(-6) M), but they were not changed by metoprolol (10(-6) M) or ICI 118.551 (10(-6) M). Formoterol and BRL 37344 increased cAMP levels. BRL 37344 increased cGMP levels in BRL 37344 group more than control group, but this increase is less significant than cAMP levels (P>0.05). Formoterol and BRL 37344 decreased amplitude of myometrial contractions with similar potency, but efficacy of formoterol was better than BRL 37344.

Investigation of the mechanism of nicotine induced relaxation in rabbit corpus cavernosum in vitro.

In order to determine whether nicotine acts on corporal smooth muscle, the mechanism of its effect on strips of rabbit corpus cavernosum was studied in vitro. Rabbit corpus cavernosum muscle strips were mounted in an organ bath with modified Krebs-Henseleit solution and aerated with 95% O(2) and 5% CO(2). Tension was measured with isometric force transducers, and muscle relaxation was expressed as the percent decrease of precontraction induced by phenylephrine. Nicotine produced concentration dependent relaxation when preparations were precontracted by phenylephrine (10(-5) M). The maximum nicotine-induced relaxation was 60.4 +/- 4.2% of the phenylephrine contraction and was not affected by indomethacin (10(-5) M), N(w)-nitro L-arginine methyl ester (3 x 10(-5) M), methylene blue (10(-5) M), glibenclamide (10(-5) M), clotrimazole (10(-6) M), tetraethylammonium (3 x 10(-4) M), or 4-aminopyridine (10(-3) M). Nicotine did not exhibit a calcium antagonizing effect. From these results, we conclude that nicotine-induced relaxation of the rabbit corpus cavernosum is not mediated by the release of nitric oxide, prostaglandins or a related substance, by the activation of potassium channels, or by the stimulation of nicotinic cholinoceptors. Further work is needed to determine the cellular mechanism(s) of the action by which nicotine acts on corporal smooth muscle.

Investigation of the mechanism of nicotine-induced relaxation on the sheep sphincter of Oddi.

Possible mechanisms for nicotine-induced relaxation were investigated in the isolated sheep's sphincter of Oddi. Sheep's sphincter of Oddi rings were mounted in tissue bath with modified Krebs-Henseleit solution and aerated with 95% oxygen and 5% carbon dioxide. Tension was measured with isometric force transducers, and muscle relaxation was expressed as percent decrease of precontraction induced by carbachol. Nicotine (1 x 10(-5) to 3 x 10(-3) mol/L) produced concentration-dependent relaxation on sphincter of Oddi precontracted by carbachol (10(-6) mol/L). Nicotine-induced relaxation was 72.8 +/- 4.2% of precontraction with carbachol (10(-6) mol/L) (mean pD2 value, 3.76 +/- 0.05 mol/L). Nicotine-induced relaxation was not affected by N(w)-nitro L-arginine methyl ester (L-NAME) (3 x 10(-5) mol/L), methylene blue (10(-5) mol/L), indomethacin (10(-5) mol/L), hexamethonium (10(-5) mol/L), glibenclamide (10(-5) mol/L), 4-aminopyridine (10(-3) mol/L), tetraethylammonium (3 x 10(-4) mol/L), clotrimazole (10(-6) mol/L), 5-nitro-2-(3-phenylpropylamino) benzoic acid (NPPB) (10(-6) mol/L), and anthracene-9-carboxylate (9-AC) (10(-6) mol/L), but potentiated by bupivacain (10(-5) mol/L). A calcium-antagonizing effect of nicotine was not observed. The results suggest that nicotine-induced relaxation of the sheep's sphincter of Oddi is not mediated by the release of prostaglandins, nitric oxide (NO), or a related substance; by the activation of potassium channels or chloride channels; or by the stimulation of nicotinic cholinoceptors. Potentiation of the nicotine-induced relaxation by bupivacain indicates that blockade of sodium channels may play a role in this relaxation.

Relaxation effects of adrenomedullin in carbachol-precontracted rabbit internal anal sphincter.

BACKGROUND: The internal anal sphincter is a specialized continuation of the circular smooth muscle layer of the rectum. It has been found that internal anal sphincter tonus is significantly increased in the majority of patients with anal fissure. Adrenomedullin has a relaxant effect on smooth muscle in different kinds of tissue. In this in vitro study, we aimed to investigate whether adrenomedullin had a relaxant effect on isolated rabbit internal anal sphincter, and the possible involvement of nitric oxide, prostaglandins, and K(+) channels. METHODS: Internal anal sphincter smooth muscle strips obtained from New Zealand rabbits were studied in vitro. The effects of adrenomedullin were investigated in isolated strips of rabbit internal anal sphincter smooth muscle precontracted with carbachol alone, and in the presence of indomethacin (a cyclooxygenase inhibitor), N(omega)-nitro- l-arginine methyl ester ( l-NAME; a nitric oxide synthetase inhibitor), and K(+) channel blockers. RESULTS: Adrenomedullin caused relaxation of the isolated precontracted rabbit internal anal sphincter strips in a concentration-dependent manner. The response of the internal anal sphincter was not affected by l-NAME, indomethacin, and the K(+) channel blockers. CONCLUSIONS: This relaxant effect of adrenomedullin might lead to novel clinical applications of adrenomedullin for anorectal disorders with increased internal anal sphincter tonus, such as anal fissure.

Effect of L-NAME on decreased ileal muscle contractility induced by peritonitis in rats.

BACKGROUND/PURPOSE: It is now well established that intestinal inflammation is associated with disturbed contractility. The aim of this study was to determine the effects of peritonitis on longitudinal ileum smooth muscle responses to KCl, carbachol and substance P (SP) and to examine the role of nitric oxide (NO) and N(omega)-nitro-L-arginine methylester (L-NAME) on ileal contractility in this peritonitis model. METHODS: Peritonitis was induced by cecal ligation and puncture (CLP) in 20 rats. While 10 of these received 1 mL distilled water as placebo, the other 10 received 5 mg/kg (subcutaneously) L-NAME before the operation. Another group of 10 rats underwent a sham operation. Twenty-four hours after the operation, the rats were killed, and their ileum was excised. Ileum segments were placed in longitudinal direction in a 10-mL organ bath; concentration-response relationship for KCl, carbachol, and SP were obtained by adding the reagent cumulatively to the bath. RESULTS: The KCl-, carbachol-, and SP-induced contractions were decreased markedly, with no change in the pD(2) values in the peritonitis group compared with controls. Peritonitis-induced changes in the contractile responses were restored significantly by in vivo L-NAME pretreatment. CONCLUSIONS: The model of CLP-induced peritonitis in rats showed that KCl-induced nonreceptor-mediated, carbachol- and SP-induced receptor-mediated contractions are significantly decreased by inflammation in the longitudinal ileum muscle. Increased synthesis of NO may be responsible for these decreases in contractile responses because they were restored significantly by in vivo L-NAME injection. Inhibition of NOS with L-NAME injection may afford a new therapeutic approach to the treatment of gastrointestinal stasis in septic patients.

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.