The effects of opioids, local anesthetics and adjuvants on isolated pregnant rat uterine muscles.

Local anaesthetics, opioids and adjuvants are often used for managing labor pain. Some others of these agents are reported to cause alterations on uterine contractility during labor. However, there are controversies and the effects of some others are unknown. In the present study, we aimed to elucidate the effects of opioids such as alfentanyl, meperidine, remifentanyl; local anesthetics such as mepivacaine, ropivacaine, bupivacaine; and adjuvants such as clonidine and midazolam on isolated pregnant rat uterine muscle. Strips of longitudinal uterine smooth muscle obtained from rats pregnant for 18-21 days were suspended in 20 ml organ baths. Isometric tension was continuously measured with an isometric force transducer connected to a computer-based data acquisition system. The effects of cumulative concentrations of alfentanyl, meperidine, remifentanyl, mepivacaine, ropivacaine, bupivacaine, clonidine and midazolam (10(-8) - 10(-4) M, for all) on contractions induced by oxytocin (1 mU/ml) were studied. Alfentanyl (10(-5) M), meperidine (10(-5) M), remifentanyl (10(-4) M), bupivacaine (10(-4) M), ropivacaine (10(-4) M) and midazolam (3 x 10(-5) M) caused significant decreases in contractile responses of uterine strips to oxytocin. Contrastingly, mepivacaine increased (33.1% +/- 7.2%) oxytocin-induced contractions of uterine strips while clonidine exerted no significant effect. The sensitivity of myometrial preparations to tested local anesthetics or opioids did not differ significantly. The findings of the present study demonstrated that some local anesthetics, opioids and adjuvants caused significant and agent-specific alterations on contractility of the pregnant rat myometrium. Therefore, they seemed to have a potential to influence uterine contractility during clinical management of pain during labor. However, further research is needed to extrapolate these finding to clinical practice.

Minimally invasive saphenous vein harvesting using a laryngoscope: procedural, functional, and morphologic evaluation.

BACKGROUND: Because commercial minimally invasive harvesting equipments significantly increase operation costs, they are not always available in all clinics worldwide. The aim of this study was to investigate whether minimally invasive saphenous vein harvesting using a laryngoscope can be applied efficiently and successfully. METHODS: Thirty patients were prospectively randomized into two groups. One group underwent a minimally invasive technique using a laryngoscope; the other, open saphenous vein harvest. A modified bridging technique, in which tissue retraction and illumination is achieved with a sterilized laryngoscope, was used for minimally invasive harvesting. Smooth muscle contractile and endothelial functions were tested in vitro using an organ chamber. Morphology was examined with light microscopy. RESULTS: There was no statistically significant difference in harvest times or length of the vein harvested by either of the above mentioned techniques. Total length of the incision in the minimally invasive group was significantly shorter than that in the open group. In follow-ups, no significant complications occurred in either group. Pain and leg edema were significantly less in the minimally invasive group compared to those of the open group. There was no significant difference in response to acetylcholine and 80 mM KCl between veins taken with the laryngoscope compared to veins taken with the traditional open technique. Similarly, histological data was unable to show any significant damage to the vessel wall. CONCLUSIONS: Because the laryngoscopic saphenectomy does not harm the harvested graft, it can be applied, instead of other minimally invasive saphenous vein harvesting systems, with a zero cost, efficiently, successfully, and with satisfactory speed and significant reduction of postoperative leg pain and wound complications.

The effect of experimental diabetes on cholinergic neurotransmission in rat trachea: role of nitric oxide.

We investigated the effect of nitric oxide (NO) on the responses of isolated tracheas to acetylcholine and to electrical field stimulation in streptozotocin-diabetic and controls rats. The contractile responses to acetylcholine were neither different nor affected by the NO synthase blocker, N(omega)-nitro-L-arginine methyl ester (L-NAME), in the two groups. Diabetic rat tracheas were supersensitive to field stimulation. L-NAME enhanced field stimulation-induced contractions at low frequencies in control rat tracheas, but had no effect in diabetic rat tracheas. After L-NAME treatment, there was no difference in sensitivity to field stimulation between the groups. The relaxation responses to sodium nitroprusside in acetylcholine-precontracted tracheas were not different between the groups. However, diabetic rat trachea was supersensitive to the relaxant effect of sodium nitroprusside on contractile responses to field stimulation. These results suggested that the increase in sensitivity to field stimulation in tracheas from diabetic rats might be due to impairment in the production and/or release of an endogenous NO-like factor.

Morphine increases plasma immunoreactive atrial natriuretic peptide levels in humans.

Plasma immunoreactive alpha-atrial natriuretic peptide (IR alpha-ANP) levels were determined before, and at 5 and 10 min after bolus intravenous administration of morphine (0.15 or 0.30 mg/kg) in 21 otherwise healthy human subjects who underwent elective surgery. Five min after injection IR alpha-ANP levels had nearly doubled in response to both doses of morphine. At 10 min, plasma IR alpha-ANP concentrations were lower than at 5 min in the 0.15 mg/kg group suggesting that IR alpha-ANP levels peak shortly after morphine administration. Morphine has been widely used in the treatment of acute left ventricular failure and ANP is a recently discovered hormone which possesses unique favourable effects in patients with congestive heart failure when administered exogenously. The combination of these data suggests an important potential role for ANP in the mechanism of action of morphine in the treatment of acute left ventricular failure.

The effect of chronic ethanol administration on nitric oxide-mediated responses in rat isolated trachea preparation.

1. In the present study, we investigated the effect of chronic ethanol administration on nitric oxide (NO)-mediated responses in rat isolated trachea preparation. 2. Ethanol was given to rats in a modified liquid diet for 21 days. Isolated tracheal rings were then used to obtain responses to electrical field stimulation (EFS) after precontraction with 100 microM histamine. The parameters of field stimulation were as follows: supramaximal voltage of 50 V, 0.5 ms duration, 10-s train; 0.5, 1, 3, 5, 10, 20, 30 and 50 Hz at 2-min intervals. The effects of L-and D-arginine (10(-6) M) on the responses to field stimulation (10-20 Hz) were studied. In other experiments, we tested the effects of N(omega)-nitro-L-arginine methyl ester (L-NAME, 10(-6)-10(-5) M) and SIN-1 (10(-6)-10(-5) M) on the responses to field stimulation. 3. Electrical field stimulation induced relaxation responses in the tracheal rings precontracted with histamine from control- and ethanol-treated rats. The relaxation responses induced by EFS were significantly reduced in the tracheal rings precontracted with histamine from ethanol dependent group. The responses induced by EFS in both groups were completely abolished by tetrodotoxin (1 microM), but unaffected by hexamethonium (1 microM). Incubation with D-arginine did not cause statistically significant increases in relaxation responses to EFS in both groups. L-Arginine (10(-6) M) caused statistically significant increases in relaxation responses to EFS in control rats, but not in ethanol dependent rats. Incubation with L-NAME (10(-6)-10(-5) M) caused statistically significant inhibition of the relaxation responses to EFS in both groups. SIN-1 (10(-6)-10(-5) M) induced significantly increase in relaxation responses to EFS in both groups. 4. Our results suggest that the possible mechanism responsible for inhibition of tracheal inhibitory responses to EFS in ethanol-dependent rats may be a reduction in production of NO and in the uptake of L-arginine.

The effect of nitric oxide synthase blockade on responses to morphine in rat aortic rings.

1 It has been suggested that opioids may play an indirect role in the regulation of the peripheral circulation through the control of nitric oxide (NO) release in vascular tissue. The current study was undertaken to investigate the effect of nitric oxide synthase (NOS) blockade on responses to morphine in phenylephrine (PE)- or KCl-precontracted rat aortic rings. 2 Morphine (3 x 10(-8) - 3 x 10(-5) M) administration did not cause any significant effect on basal tonus of endothelium-intact or endothelium-denuded preparations. Morphine produced concentration-dependent relaxation responses in endothelium-intact as well as in endothelium-denuded rat aortic rings precontracted by PE or KCl. Removal of endothelium did not significantly alter the relaxation responses to morphine. 3 The relaxant responses to morphine were significantly and partially inhibited by pretreatment of tissues with naloxone (NAL, 3 x 10(-5) M) for 5 min. The inhibitory effect of NAL on relaxant responses to morphine in PE- or KCl-precontracted rings did not differ significantly between endothelium-intact and endothelium-denuded preparations. 4 Incubation of endothelium-intact or endothelium-denuded rat aortic rings with NOS inhibitor, Nomega-nitro-L-arginine methyl ester (L-NAME, 10(-4) M) for 20 min did not cause a significant inhibition on relaxation responses to morphine. 5 These findings confirmed the presence of opiate receptors in rat thoracic aorta, but suggested that mechanisms other than NO release play a role in the relaxant effect of morphine on rat aortic rings.

The effects of selective phosphodiesterase III and V inhibitors on adrenergic and non-adrenergic, non-cholinergic relaxation responses of guinea-pig pulmonary arteries.

1. The aim of the present study was to investigate the role of several possible neurotransmitters in mediating non-adrenergic, non-cholinergic (NANC) relaxation, and the effects of phosphodiesterase (PDE) III and V inhibitors on adrenergic and NANC relaxation in branch pulmonary artery (PA) of guinea-pig. 2. Under the NANC conditions, electrical field stimulation (EFS, 60 V, 0.2 ms, 20 Hz) induced a tetrodotoxin-sensitive relaxation of the histamine-precontracted PA rings. The nitric oxide (NO) synthase inhibitor NG-nitro-l-arginine methyl ester (l-NAME, 10(-4) m) and the guanylyl cyclase inhibitor 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ, 10(-5) m) partially inhibited the EFS-induced relaxation. The inhibitory effect of l-NAME was reversed completely by l-arginine (10(-3) m), but not d-arginine (10(-3) m). 3. This NANC relaxation was attenuated by 8-phenyltheophylline (10(-5) m), a P1-purinoceptor antagonist. 4. The NANC response was potentiated by 10-6 m zaprinast, a type V PDE inhibitor, but was unaffected by 3 x 10-6 m milrinone, a type III PDE inhibitor. 5. Sodium nitroprusside (SNP) caused a concentration-dependent vasodilator effect which was potentiated by zaprinast, but unaffected by milrinone. Moreover, the effect of combination of zaprinast with milrinone was not significantly different from that observed with zaprinast alone. 6. Isoprenaline produced a concentration-dependent vasodilatation in branch PA of guinea-pig which was potentiated by both zaprinast and milrinone, the efficacy of milrinone being greater than zaprinast. 7. These results suggest that both nitrergic and purinergic pathways are involved in mediating the NANC relaxation in branch PA of guinea-pig. The combination of PDE III or V inhibitors with vasorelaxant drugs may be a hopeful approach for the treatment of pulmonary hypertension.

Pentoxifylline-induced vasodilatation is not endothelium-dependent in rabbit aorta.

It is well known that phosphodiesterase inhibitors, such as MB 22948 or papaverine, induce endothelium-dependent relaxation by potentiating the effects of endothelium-derived relaxing factor released spontaneously in vascular tissues. The present study was planned to determine whether the vasodilator properties of pentoxifylline, a phosphodiesterase inhibitor, are endothelium-dependent and modulated by its phosphodiesterase inhibitory activity in rabbit aorta. In opened aortic rings precontracted with phenylephrine (0.5 microM), pentoxifylline (1 microM-1 microM) caused concentration-dependent relaxation. Pentoxifyl line-induced relaxation was not modified by incubation with methylene blue (10 microM) or NG-nitro-L-arginine methyl ester (0.1 microM), or by mechanical denudation of endothelium. Forskolin (1nM-0. 1mM) and sodium nitroprusside (10nM-0. 1mM) induced concentration-dependent relaxations in both endothelium containing and endothelium denuded preparations. The relaxation induced by forskolin and sodium nitroprusside, which are cyclic AMP and cyclic GMP mediated, respectively, and which are both endothelium-independent, were not altered after incubation with pentoxifylline (0.1 mM) for 30 min. In conclusion, our experiments suggest that the vasodilator properties of pentoxifylline in isolated rabbit aorta are primarily at the level of the vascular smooth muscle and may not involve EDRF or its phosphodiesterase inhibitory activity.

[The pharmacological effect of Yersinia enterocolitica (O) antigens on isolated guinea pig and rabbit ileum]. / Yersinia enterocolitica (O) antijeninin izole kobay ve tavsan ileumuna farmakolojik etkisi.

In this study, acetylcholine-like effect of Yersinia enterocolitica (O) antigen on isolated guinea-pig and rabbit ileum was observed. Atropine was shown its antagonist.

The effect of benfotiamine on mu-opioid receptor mediated antinociception in experimental diabetes.

Diabetic neuropathy is a prevalent, disabling disorder. Currently, the only treatments available to patients with diabetic neuropathy are glucose control and pain management. B vitamin present neuroprotective effects, which are suggested to be related to their analgesic action in various models of neuropathic pain. According to our literature knowledge there is no report about antinociceptive effects of thiamine as benfotiamine and opioids together in diabetic mice. The purpose of this study was to determine the effects of benfotiamine on the antinociception produced by mu-opioid receptor agonist fentanyl in diabetic mice. The effects of benfotiamine on antinociception produced by fentanyl in diabetic mice were studied in 4 groups. Antinociceptive effect was determined with tail flick, hot plate and formalin test. Our results showed that, mu-opioid agonist fentanyl in benfotiamine applied diabetic group caused more potent antinociceptive effect than in diabetic group without benfotiamine treatment. In brief benfotiamine supplement in diet did not bring out antinociceptive effect itself, but during development of STZ diabetes, benfotiamine replacement increased the antinociceptive effect of fentanyl in mice tail-flick test. This effect is probably due to the replacement of benfotiamine efficiency occurring in diabetes mellitus. Finally, we suppose that oral benfotiamine replacement therapy may be useful to ameliorate analgesic effect of mu-opioid agonists on neuropathic pain in diabetic case.

Experimental hyperhomocysteinemia disturbs bone metabolism in rats.

OBJECTIVE: To investigate whether experimental hyperhomocysteinemia (HHCY) can induce adverse changes in bone metabolism. METHODS: Blood and urine samples were collected from rats fed with a methionine-enriched diet (HHCY, n = 18) or an isocaloric control diet (control, n = 10) for 12 weeks. Biochemical bone turnover markers (osteocalcin, hydroxyproline, N-terminal collagen I telopeptides and homocysteine (HCY), folate and vitamin B12) were measured. Whole body bone mineral density (BMD) was assessed by dual energy X-ray absorptiometry. RESULTS: HCY was significantly higher in HHCY than in control rats (16.2 versus 3.2 micromol/L; p = 0.0006). Bone resorption parameters hydroxyproline (1.60 +/- 0.6 versus 0.85 +/- 0.4; p<0.05) and N-terminal collagen I telopeptides (150.8 +/- 78 versus 48.1 +/- 26 nmol/L BCE; p<0.05) increased, whereas bone formation marker osteocalcin (9.01 +/- 3.8 versus 15.07 +/- 4.2 ng/mL; p<0.05) decreased in HHCY compared to control rats. The relation N-terminal collagen I telopeptides/osteocalcin significantly increased in HHCY compared to control rats (13.14 +/- 3.1 versus 4.14 +/- 1.9). BMD measurement did not reveal any differences between groups. CONCLUSION: These findings demonstrate a significant modification of bone turnover in HHCY rats. The relation between bone resorption and formation indicates a shift toward bone resorption, which might be a plausible explanation for the relation between HHCY and fracture risk.

France: late abortion.

PIP: In France, under the terms of a law passed by Parliament in 1975, a woman may have an abortion up to 12 weeks of pregnancy if she is a French resident and, in the event that she is a minor, she has parental consent. The woman must also have 2 medical consultations, a week apart. The woman is reimbursed by the state up to 70% of the cost of the abortion. After 12 weeks, abortion, except for therapeutic abortion, under the terms of Article 317 of the Criminal Code, is a crime, punishable by 6 months to 10 years in prison, a fine of between 1800 and 250,000 Francs, and loss of professional license. Moreover, Article 647 of the Health Code bans any advertising, incitement or propaganda for abortion or abortion-inducing products. Many French women go to Britain or Holland for abortions after 12 weeks, but they face the financial burden of traveling as well as the difficulties of getting help in a strange country and the stigma of having done something illegal. The Mouvement Francais pour le Planning Familial, which won the legalization of contraception in 1967, is now fighting for legal abortion as well as the distribution of information about sexuality, contraception, and abortion in the schools. 2 charges of incitement to abortion have been brought against the organization.^ieng

Comparison of the effects of selective III, IV and nonselective phosphodiesterase inhibitors on isolated tracheal preparations in streptozotocin-diabetic rats.

The aim of the present study was to investigate the relaxant effects of selective III, IV and nonselective phosphodiesterase inhibitors, e.g. amrinone, rolipram and theophylline, respectively, on isolated tracheal preparations in streptozotocin (STZ)-diabetic rats. Six weeks before the experiments, the rats to be made diabetic were anesthetized with diethyl ether and diabetes was then induced by a single intravenous injection of STZ (65 mg kg(-1)) via the tail vein. All drugs produced concentration-dependent relaxations of tracheal preparations precontracted with 10(-6) mol/l carbachol. The responses of phosphodiesterase inhibitors were marked in the diabetic groups compared to the control group, but it was found that only amrinone responses are significantly higher in the diabetic groups.

Evidence that nitric oxide mediates non-adrenergic non-cholinergic relaxation induced by GABA and electrical stimulation in the rat isolated duodenum.

1. GABA (3 x 10(-4) M) and electrical stimulation (60 mV, 1 ms, 0.1 Hz) produced a non-adrenergic non-cholinergic (NANC) relaxation response in the rat isolated duodenum. 2. Tetrodotoxin (10(-6) M) incubation abolished GABA and electrical stimulation responses but not ATP (10(-3) M)-induced relaxation. 3. Desensitization to ATP (10(-3) M) or alpha, beta-methylene ATP (10(-5) M) and incubation with the P1 receptor antagonist 8-phenyltheophylline (10(-5) M) failed to affect relaxation induced by GABA and low frequency electrical stimulation. 4. The inhibitor of L-arginine-NO synthase N omega-Nitro-L-arginine methyl ester (L-NAME) (10(-4)-3 x 10(-4) M) reduced the NANC relaxations elicited by GABA and low frequency electrical stimulation in a dose-dependent manner. These effects were partially reversed by the addition of L-arginine (10(-3)-3 x 10(-3) M). ATP (10(-3) M)-induced relaxations were not modified by L-NAME (3 x 10(-4) M) incubation. 5. These results suggest that nitric oxide is involved in inhibitory NANC transmission in the rat duodenum. We provided original evidence that nitric oxide is involved in neurally mediated relaxations induced by GABA in rat isolated duodenum.

Cardiovascular effects of intrathecally injected mu, delta and kappa opioid receptor agonists in rabbits.

1. Intrathecal saline, the mu opioid agonist [D-Ala2, MePhe4, Gly5-ol] enkephalin (DAGO) and delta opioid agonist [D-Pen2, D-Pen5] enkephalin (DPDPE) had no significant effects on systemic blood pressure and heart rate values. 2. The kappa opioid agonist bremazocine however, caused falls in blood pressure and reduction in heart rate. 3. Intrathecal administration of saline, DPDPE and bremazocine had no effect on baroreflex sensitivity. 4. Intrathecal administration of DAGO caused a reduction in baroreflex sensitivity; this effect was inhibited by naloxone and abolished after atenolol. 5. The role of spinal opioid systems as a possible site of action is discussed.

Exogenous adenosine potentiates hypnosis induced by intravenous anaesthetics.

We investigated the effect of adenosine on hypnosis induced by thiopentone, propofol and midazolam in mice. The onset and duration of hypnosis were determined by the loss of righting reflex. Adenosine and 2-chloroadenosine caused a significant shortening of onset of sleep-time and prolongation of duration of sleep-time in all groups (p < 0.05). Dipyridamole administration before combined intravenous anaesthetic-adenosine or intravenous anaesthetic-2-chloroadenosine administration produced similar effects to adenosine (p < 0.05). The adenosine antagonist theophylline, given before intravenous anaesthetic-adenosine or intravenous anaesthetic-2-chloroadenosine administration caused a significant delay in onset of sleep-time and shortening in the duration of sleep-time (p < 0.05). We conclude that central excitatory noradrenergic neurones play an important role in adenosine, 2-chloroadenosine and dipyridamole-induced hypnotic responses to intravenous anaesthetics and their inhibition by adenosine antagonists.

Impairment of GABA-mediated contractions of rat isolated ileum by experimental diabetes.

The effect of diabetes induced by pretreatment with streptozotocin 6 weeks prior to the study on the responses induced by gamma-aminobutyric acid (GABA), the GABA(A) agonist 3-aminopropane sulfonic acid (3-APS), and acetylcholine in the rat isolated ileum was evaluated. GABA, 3-APS, and acetylcholine showed a rightward shift in their concentration-dependent effects in the ileum that also attained a lower maximum in streptozotocin-diabetic rats as compared with control rats (p < 0.05). It is suggested that the reduced contractile responses of ileal smooth muscle to GABA and 3-APS might be due to a direct effect of diabetes on the GABAergic system or to its effect on the cholinergic system.

Beneficial effects of pentoxifylline on cyclosporine-induced nephrotoxicity.

1. Hypertension and renal failure are the two most common and severe complications due to cyclosporine A (CsA) therapy after transplantation. To determine whether an in vivo treatment with pentoxifylline (PTX) can prevent the toxic effects of CsA, three groups of rats were studied. 2. The first group of rats (n = 11) received daily injections of CsA (15 mg/kg, i.m.) and PTX (45 mg/kg, i.p., b.i.d.), the second group of rats (n = 11) was treated with CsA only and the third group of rats (n = 11) served as the control group (vehicle treatment). 3. Whole blood CsA levels were similar in CsA + PTX and CsA alone groups. Although CsA treatment significantly increased mean arterial blood pressure (110.00 +/- 2.48 mmHg; P < 0.01), there was no significant increase in the PTX co-treated group (104.09 +/- 2.96 mmHg) compared with initial values. In both the CsA alone and CsA + PTX groups the heart rate (365.45 +/- 6.65 and 357.27 +/- 7.23 b.p.m., respectively; P < 0.05) were found to be significantly higher than initial values. Serum creatinine levels increased significantly in the CsA alone group (1.40 +/- 0.11 mg/dL; P < 0.01) compared with control values (0.81 +/- 0.04 mg/dL). This increase was prevented by co-treatment with PTX (serum creatinine 1.11 +/- 0.01 mg/dL; P < 0.05). Total [99mTc]-DTPA percentage renal uptake, as an index of glomerular filtration rate (GFR), was markedly and significantly lower in the CsA alone group (10.01 +/- 0.79%; P < 0.01) than in the control group (18.19 +/- 1.32%). Pentoxifylline co-treatment attenuated this decrease compared with GFR in the CsA alone group (13.00 +/- 0.75%; P < 0.01). 4. These results suggest that the co-administration of PTX with CsA may prevent the dose-limiting toxic effects of CsA therapy.

Effect of experimental diabetes on GABA-mediated inhibition of neurally induced contractions in rat isolated trachea.

1. In the present study, we investigated the effect of GABA and selective GABA agonists and antagonists on neurally induced tracheal contractions in streptozotocin (STZ) diabetic rats. 2. Contractile responses to electrical field stimulation (EFS) in rat tracheal rings were completely abolished by atropine and tetrodotoxin, but were unaffected by the ganglion blocker hexamethonium, indicating that they were mediated via neuronal release of acetylcholine (ACh). 3. Contractions induced by EFS, but not by exogenous ACh, were inhibited by GABA and the selective GABA(B) receptor agonist baclofen, but not by the selective GABA(A) receptor agonist 3-aminopropane sulphonic acid. The inhibitory effects of GABA or baclofen were not affected by the GABA(A) antagonist bicuculline, but were significantly reversed by the GABA(B) antagonist phaclofen. 4. The inhibitory effects of both GABA and baclofen were found to be significantly greater in trachea from control rats compared with tissues from diabetic rats. 5. Non-adrenergic, non-cholinergic relaxation responses elicited by EFS in precontracted tracheal rings from diabetic and control rats were similar in magnitude and were unaffected by GABA or GABA analogues. 6. These results suggest that GABA decreases the response to EFS by directly inhibiting the evoked release of ACh through GABA(B) receptors in rat trachea and that STZ-induced diabetes causes an impairment in the inhibitory effect of GABA on neurally induced contractions in this tissue.

Effects of diabetes on non-adrenergic, non-cholinergic relaxation induced by GABA and electrical stimulation in the rat isolated duodenum.

1. The effects of streptozotocin (STZ)-induced experimental diabetes on nitrergic-mediated responses to GABA and electrical field stimulation (EFS) have been evaluated in rat isolated duodenum. 2. In the presence of noradrenergic and cholinergic blockade, EFS (60 V, 1 ms, 0.1-32 Hz) induced frequency dependent relaxations of the preparation. GABA also caused submaximal relaxation of the rat duodenum. The relaxations induced by GABA and EFS were reduced in duodenal tissues from diabetic rats compared with control rats. 3. Neither ATP- nor sodium nitroprusside-induced relaxations were altered in diabetic duodenal tissues. GABA- and EFS-induced relaxations were inhibited by NG-nitro-L-arginine methyl ester (L-NAME; 300 mmol/L) in both diabetic and control rats. Although the inhibition caused by L-NAME of GABA- and EFS-induced relaxation was partially reversed by L-arginine (1 mmol/L), L-arginine alone had no effect on GABA- and EFS-induced relaxation in diabetic rats. 4. These results suggest that STZ-induced diabetes impairs non-adrenergic, non-cholinergic relaxation induced by EFS and GABA. Impairment of nitrergic innervation of the rat duodenum may contribute to the abnormalities of intestinal motility abnormalities associated with diabetes.