Effects of intracerebroventricularly injected glucagon-like peptide-2 on ethanol-induced gastric mucosal damage in rats.

PURPOSE: The present study aims to investigate the effects of intracerebroventricularly (i.c.v.)-injected glucagon-like peptide-2 (GLP-2) on ethanol-induced gastric mucosal damage and to reveal the mechanisms involved in this effect. MATERIALS AND METHODS: Rats received absolute ethanol orally via an orogastric tube 30 minutes after GLP-2 (1-200 ng/10 µl; i.c.v.) or saline (10 µl) injections. They were decapitated 1 hour later, their stomachs were removed, and the gastric mucosal damage was scored. RESULTS: A total of 100 ng GLP-2 inhibited the gastric mucosal damage by 67%. This effect was abolished by the calcitonin gene-related peptide (CGRP) receptor antagonist CGRP-(8-37) (10 µg/kg; s.c.), but was not affected by either the nitric oxide (NO) synthase inhibitor L-NAME (30 mg/kg; s.c.) or the cyclooxygenase inhibitor indomethacin (5 mg/kg; i.p.). The most effective gastroprotective dose of GLP-2 (100 ng/10 µl; i.c.v.), but not the higher doses (150 or 200 ng/10 µl; i.c.v.) prevented the decrease in gastric mucosal blood flow caused by ethanol. In conclusion, i.c.v. GLP-2 protects against ethanol-induced gastric mucosal damage and this effect is mediated by CGRP receptor activation and gastric mucosal blood flow, but not by NO or prostaglandins.

Immediate and delayed treatment with gabapentin, carbamazepine and CNQX have almost similar impact on cognitive functions and behavior in the lithium-pilocarpine model in rats.

In the present study, we aimed to investigate the effects of immediate and delayed treatment with intracerebroventricular (i.c.v.) gabapentin (GBP), carbamazepine (CBZ) and 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) on learning and memory, anxiety, and locomotor activity in rats with lithium-pilocarpine-induced status epilepticus (SE). SE was induced by intraperitoneal injections of 3mEq/kg LiCl followed by 45mg/kg pilocarpine 24h later. In the first series of experiments, rats were divided into four groups three hours after the onset of SE and received GBP (100µg/10µl, two times a day; i.c.v.), CBZ (200µg/10µl; i.c.v.), CNQX (25nmol/10µl; i.c.v.) or saline (10µl; i.c.v.) for 7days. Six weeks after SE, cognitive and behavioral performances were evaluated by Morris water maze, elevated plus maze, and open field tests. In the second series, rats received no treatment for six weeks following SE. On the seventh week the same treatment with the previous rats was given and six weeks later the cognitive and behavioral tests were applied. SE significantly impaired spatial learning and memory in the Morris water maze. GBP treatment improved the acqusition and memory performance. CNQX worsened the acqusition but improved the memory performance, while CBZ worsened both parameters. In the elevated plus maze, epileptic rats which received saline showed significantly lower anxiety levels with respect to the naive rats. Only CBZ led to further anxiolysis, while the other drugs had no effect. Locomotor activity significantly increased due to SE, which was augmented by GBP and CNQX. The impact of immediate and delayed treatment with these drugs on cognition and behavior seems to be quite similar.

Effects of centrally injected glucagon-like peptide-2 on gastric mucosal blood flow in rats: possible mechanisms.

"Glucagon-like peptide-2" (GLP-2) is a peptide that is released from the enteroendocrine L cells in response to food in the gastrointestinal tract. Peripheral injection of GLP-2 has been shown to increase gastrointestinal blood flow, but effects of central GLP-2 on any vascular bed has not been studied yet. The aim of this study is to investigate the effects of various doses of intracerebroventricularly (i.c.v.)-injected GLP-2 on gastric mucosal blood flow (GMBF) and contribution of calcitonin gene related peptide (CGRP), nitric oxide synthase-nitric oxide (NOS-NO) and cyclooxygenase-prostaglandin (COX-PG) systems to the possible effect. The gastric chamber technique was used to determine GMBF. Urethane anesthesia was used throughout the recording procedure. Male Wistar rats were treated with GLP-2 (100, 150 ve 200ng/10µl; i.c.v.) or saline (10µl; i.c.v.) in order to find out the effective dose of i.c.v. GLP-2 on GMBF. Then, CGRP receptor antagonist CGRP-(8-37) (10µg/kg; s.c.), NOS inhibitor NG-nitro-l-arginine methyl ester (l-NAME; 30mg/kg; s.c.) or COX inhibitor indomethacin (5mg/kg; i.p.) was injected before the effective dose of i.c.v. GLP-2. GMBF was measured continuously for 35min following GLP-2 and recorded every fifth minute. Non-parametric Kruskal-Wallis test was used for statistical analysis. Differences were considered to be significant at p<0.05. GMBF increased rapidly following 100ng GLP-2 injection and did not fall to the basal levels during 35min. Other doses of i.c.v. GLP-2 did not produce any significant difference in GMBF. CGRP receptor antagonist, CGRP-(8-37) (10µg/kg; s.c.) and COX inhibitor indomethacin (5mg/kg; i.p.) significantly prevented the increase in GMBF due to GLP-2 (100ng; i.c.v.), while l-NAME (30mg/kg; s.c.) was ineffective. None of the drugs produced a significant change in GMBF when administered alone. Thus we suggest that, i.c.v. GLP-2 increases GMBF and CGRP and endogenous prostaglandins but not NO, contribute to this effect.

WITHDRAWN: Effects of centrally-injected glucagon-like peptide-2 on gastric mucosal blood flow in rats; possible mechanisms.

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Effects of systemic chlorogenic acid on random-pattern dorsal skin flap survival in diabetic rats.

There has been considerable interest in understanding the effects of antioxidants in flap survival during diabetes. Previous studies showed that chlorogenic acid (CGA) exhibits potent antioxidant effects. We aimed to determine the effects of systemic CGA treatment on skin flap survival in an experimental random-pattern dorsal skin flap model in diabetic rats. Twenty-eight male Wistar rats were divided into four groups: phosphate buffered saline (PBS)-treated or CGA-treated nondiabetic rats, PBS-treated or CGA-treated diabetic rats. Diabetes was induced by streptozotocin (45 mg/kg). Caudally based bipedicled dorsal skin flaps were elevated. CGA (100 mg/kg) or PBS (mL/kg; as vehicle) was administered intraperitoneally once daily. On postoperative day 7, flap survival, regional blood perfusion and microangiography were evaluated. The malondialdehyde (MDA), reduced glutathione (GSH), superoxide dismutase (SOD) and nitric oxide (NO) levels were evaluated from the flap tissue. Capillary density and vascular endothelial growth factor (VEGF) expression were assessed. Harmful effects of diabetes on flap survival were observed. CGA attenuated these effects and allowed greater survival and blood perfusion. CGA decreased MDA and NO levels and increased GSH and SOD levels. CGA elevated capillary density and VEGF expression. This study showed that peripherally administered CGA significantly improved flap survival in diabetic and nondiabetic rats.

Role of central arginine vasopressin receptors in the analgesic effect of CDP-choline on acute and neuropathic pain.

Recent studies have demonstrated that arginine vasopressin (AVP) plays a crucial role in pain modulation. In addition, our previous studies have proven that centrally administered cytidine-5'-diphosphate-choline (CDP-choline; citicoline) elicits an analgesic effect in different pain models in rats. Given that CDP-choline enhances central and peripheral vasopressin levels, the present study was designed to investigate the role of central AVP receptors in the analgesic effect of CDP-choline in acute and chronic constriction injury-induced neuropathic pain models. For this purpose, rats were pretreated intracerebroventricularly with the AVP V1 or AVP V2 receptor antagonist 15 min before intracerebroventricular injection of CDP-choline or saline, and pain threshold was determined using the Randall-Selitto test. AVP V1 and AVP V2 receptor antagonist blocked the CDP-choline-induced analgesic effect either in acute or neuropathic models of pain in rats. These results suggest, for the first time, that central AVP receptors are involved in the CDP-choline-elicited analgesic effect.

Hemostatic effect of a chitosan linear polymer (Celox®) in a severe femoral artery bleeding rat model under hypothermia or warfarin therapy.

BACKGROUND: In this study, the hemostatic efficacy of Celox® in rats under hypothermia or warfarin treatment was investigated. METHODS: A total of forty-eight Sprague-Dawley female rats weighing 200-350 g were used in the study. Six experimental study groups were designed, as follows: Group 1: Normothermia + compression; Group 2: normothermia + Celox®; Group 3: hypothermia + compression; Group 4: hypothermia + Celox®; Group 5: normothermia + warfarin + compression; and Group 6: normothermia + warfarin + Celox®. RESULTS: Celox® provided effective hemorrhage control in all three tested groups. There was a statistically significant difference between compression and Celox® implementation in all groups in terms of hemostasis (p-values for the normothermia, hypothermia and warfarin groups were p<0.05, p<0.01 and p<0.01, respectively). Furthermore, the compression numbers were significantly lower in all of the groups that received Celox ® than in those in which compression alone was applied (p-values for the normothermia, hypothermia and warfarin groups were p<0.01, p<0.01 and p<0.001, respectively). CONCLUSION: Celox® provides effective hemorrhage control under conditions of normothermia, hypothermia and use of the oral anticoagulant agent warfarin.

Effects of centrally-injected glucagon-like peptide-1 on pilocarpine-induced seizures, anxiety and locomotor and exploratory activity in rat.

Glucagon-like peptide-1 (7-36)-amide (GLP-1) is a gut peptide, which exerts significant effects on glucose homeostasis. GLP-1 and GLP-1 receptors are also widely distributed in the central nervous system. In the present study, we aimed to investigate the effects of intracerebroventricularly (i.c.v.)-injected GLP-1 on pilocarpine-induced seizures, anxiety and locomotor and exploratory activity in rat. Rats were pretreated with GLP-1 (1-1000 ng/5 microl; i.c.v.) or saline (5 microl; i.c.v.) 30 min before seizure induction by pilocarpine (2.4 mg/5 microl; i.c.v.) and with GLP-1 (1, 10, 100 ng/5 microl; i.c.v.) or saline (5 microl; i.c.v.) 30 min before the open field test or the elevated plus maze test. GLP-1 did not produce any protective effect against pilocarpine-induced seizures and did not also produce statistically significant differences in the number of squares visited (measure of locomotor activity) or number of rearings (measure of exploratory behaviour), compared to the saline-treated rats in the open field test. On the other hand, GLP-1 (1 ng and 10 ng; i.c.v.) induced an anxiogenic effect, indicated by a decrease in the time spent in open arms, an increase in the time spent in closed arms, and a decrease in the anxiety scores in the elevated plus maze test. Pretreatment with an arginine vasopressin (AVP) V(1) receptor antagonist (125 ng/5 microl; i.c.v.) and L-NAME (100 microg/5 microl and 200 microg/5 microl) significantly abolished the anxiogenic effect of GLP-1 (1 ng/5 microl; i.c.v.). These results suggest that, centrally-injected GLP-1 produces anxiogenic effects via NO pathway and AVP V(1) receptors, but does not have any effects on pilocarpine-induced seizures or locomotor and exploratory activity in the open field test.

Effect of peripherally-injected glucagon-like peptide-1 on gastric mucosal blood flow.

The aim of this study was to investigate the mechanisms involved in the effect of glucagon-like peptide-1 (GLP-1) on the decrease in gastric mucosal blood flow (GMBF) induced by intragastric ethanol. After preparation of the stomach for GMBF recording, a probe was placed to the gastric mucosa and basal GMBF recordings were obtained by a laser Doppler flowmeter after a 30-minute stabilization period. Following GLP-1 (1000 ng/kg; i.p.) injection, 1 ml of absolute ethanol was applied to the gastric chamber and GMBF was recorded continuously during a 30-minute period. GLP-1 (1000 ng/kg; i.p.) prevented the decrease in GMBF induced by ethanol. Nitric oxide (NO) synthase inhibitor L-NAME, (30 mg/kg; s.c.), calcitonine gene-related peptide (CGRP) receptor antagonist CGRP-(8-37) (10 microg/kg; i.p.), and cyclooxygenase inhibitor indomethacin (5 mg/kg; i.p.) all inhibited the GMBF-improving effect of GLP-1. We concluded that, NO, CGRP and prostaglandins may be involved in the effect of peripherally-injected GLP-1 on GMBF reduction induced by intraluminal ethanol.

Peripheral GLP-1 gastroprotection against ethanol: the role of exendin, NO, CGRP, prostaglandins and blood flow.

The aim of this study was to investigate the effects of peripherally injected glucagon like peptide-1 (GLP-1) on ethanol-induced gastric mucosal damage and the mechanisms included in the effect. Absolute ethanol was administered through an orogastric cannula right after the injection of GLP-1 (1, 10, 100, 1000 or 10,000 ng/kg; i.p.). The rats were decapitated an hour later, the stomachs removed and the gastric mucosal damage scored. 1000 ng GLP-1 inhibited gastric mucosal damage by 45% and 10,000 ng GLP-1 by 60%. The specific receptor antagonist exendin-(9-39) (2500 ng/kg; i.p.), calcitonin gene related peptide (CGRP) receptor antagonist CGRP-(8-37) (10 microg/kg; i.p.), nitric oxide (NO) synthase inhibitor l-NAME (30 mg/kg; s.c.) and cyclooxygenase inhibitor indomethacin (5 mg/kg; i.p.) inhibited the preventive effect of GLP-1 on ethanol-induced gastric mucosal damage. GLP-1 also prevented the decrease in gastric mucosal blood flow caused by ethanol when administered at gastroprotective doses (1000 and 10,000 ng/kg; i.p.). In conclusion, GLP-1 administered peripherally prevents the gastric mucosal damage caused by ethanol in rats. CGRP, NO, prostaglandin and gastric mucosal blood flow are thought to play a role in this effect, mediated through receptors specific to GLP-1.

Central choline suppresses plasma renin response to graded haemorrhage in rats.

Central administration of choline increases blood pressure in normotensive and hypotensive states by increasing plasma concentrations of vasopressin and catecholamines. We hypothesized that choline could also modulate the renin-angiotensin pathway, the third main pressor system in the body. Plasma renin activity (PRA), which serves as an index of the function of the peripheral renin-angiotensin system, was determined in rats subjected to graded haemorrhage following central choline administration. Intracerebroventricular (i.c.v.) injection of choline (12.5-150 microg), a precursor of the neurotransmitter acetylcholine (ACh), inhibited the increase in PRA in rats subjected to graded haemorrhage by sequential removal of 0.55 mL blood/100 g bodyweight. Choline, in the range 50-150 microg, increased blood pressure. Intraperitoneal (i.p.) administration of 150 microg choline failed to alter blood pressure and plasma renin responses to graded haemorrhage. Administration of a higher dose (90 mg/kg, i.p.) of choline decreased blood pressure and enhanced PRA in the first two blood samples obtained during the graded haemorrhage. Physostigmine (10 microg, i.c.v.), ACh (10 microg, i.c.v.), carbamylcholine (10 microg, i.c.v.) and cytidine 5'-diphosphocholine (CDP-choline; 250 microg, i.c.v.) increased blood pressure and attenuated plasma renin responses to graded haemorrhage. Inhibition of PRA by i.c.v. choline was abolished by i.c.v. pretreatment with mecamylamine (50 microg), but not atropine (10 microg). Blood pressure responses to choline (150 microg) were attenuated by pretreatment with both mecamylamine and atropine. Inhibition of PRA in response to central choline administration was associated with enhanced plasma vasopressin and catecholamine responses to graded haemorrhage. Pretreatment of rats with a vasopressin antagonist reversed central choline-induced inhibition of plasma renin responses to graded haemorrhage without altering the blood pressure response. In conclusion, central administration of choline inhibits the plasma renin response to graded haemorrhage. Nicotinic receptor activation and an increase in plasma vasopressin appear to be involved in this effect.

Central effects of glucagon-like peptide-1 on cold-restraint stress-induced gastric mucosal lesions.

BACKGROUND/AIMS: Intracerebroventricular (i.c.v.) glucagon-like peptide-1 (GLP-1) has been shown to prevent gastric mucosal lesions induced by reserpine and ethanol. Here, we aimed to investigate the effects of i.c.v. GLP-1 on stress-induced gastric mucosal lesions and the mechanisms which may mediate these effects. METHODS: Rats were equipped with intravenous and i.c.v. cannulas under ether anesthesia. To induce cold-restraint stress, rats were kept individually in wire cages, specifically prepared according to their sizes, at 7-9 degrees C for 5 hours. They were then decapitated, and their stomachs were removed and scored for mucosal damage. GLP-1 (1, 10, 100, 1000 ng/10 microl; i.c.v.) was injected 5 min before cold-restraint stress induction. Rats were pretreated with exendin-(9-39) (2.5 ng/10 microl; i.c.v. and 250 ng/kg; intraperitoneal [i.p.]), calcitonin gene-related peptide (CGRP)-(8-37) (10 microg/kg; i.p.), N(G)-nitro-L-arginine methyl ester (L-NAME) (3 mg/kg; i.v.), indomethacin (5 mg/kg; i.p.) and atropine (1 mg/kg; i.p.) to investigate mechanisms which may mediate the gastroprotective effect of GLP-1. RESULTS: GLP-1 (1000 ng/10 microl; i.c.v.) significantly prevented gastric mucosal lesions induced by cold-restraint stress (p<0.01). Intracerebroventricular (i.c.v.), but not i.p., injection of exendin-(9-39) significantly blocked the gastroprotective effect of the peptide (p<0.05). Pretreatment with CGRP-(8-37), L-NAME and indomethacin also prevented the gastroprotective effect of i.c.v. GLP-1 (p<0.05, p<0.05 and p<0.01, respectively), while pretreatment with atropine did not prevent the gastroprotective effect of the peptide. CONCLUSIONS: We conclude that i.c.v GLP-1 inhibits the gastric mucosal damage induced by cold-restraint stress via the activation of its specific receptors, and CGRP, nitric oxide and prostaglandins, but not cholinergic muscarinic receptors, mediate this effect.

Protective effect of centrally-injected glucagon-like peptide-1 on reserpine-induced gastric mucosal lesions in rat: possible mechanisms.

BACKGROUND/AIMS: Intracerebroventricular glucagon-like peptide- 1 (GLP-1) has been shown to prevent the gastric mucosal lesions induced by reserpine. In the present study, we aimed to investigate the contribution of 1- the cholinergic pathway, 2- the sympathetic pathway, 3- somatostatin and 4- endogenous nitric oxide to this gastroprotective effect. METHODS: Rats were equipped with intravenous and intracerebroventricular cannulas under ether anesthesia for drug delivery. Rats were pretreated with mecamylamine (5 mg/kg; i.p.) and atropine sulfate (1 mg/kg; i.p.), yohimbine (1 mg/kg; i.p.), cysteamine (280 mg/kg; s.c.), and NG-nitro-L-arginine methyl ester (3 mg/kg; i.v.) to investigate the role of the cholinergic pathway, sympathetic pathway, somatostatin and endogenous nitric oxide, respectively, in the gastroprotective effect of GLP-1. To produce gastric mucosal lesions, reserpine was administered intraperitoneally at a dose of 25 mg/kg in 10 ml/kg of 0.5% acetic acid solution. Four hours later, the animals were decapitated, and their stomachs were removed and scored for mucosal damage. RESULTS: Glucagon- like peptide-1 (100 ng/10 microl; i.c.v.) inhibited the reserpine-induced gastric mucosal damage by 90% (p<0.01). Neither the nicotinic receptor antagonist mecamylamine (5 mg/kg; i.p.) nor the muscarinic receptor antagonist atropine sulfate (1 mg/kg; i.p) affected the gastroprotective activity of GLP-1. On the other hand, pretreatment with yohimbine, an alpha2-adrenergic receptor antagonist (1 mg/kg; i.p.), cysteamine, a somatostatin depletor (280 mg/kg; s.c.), and NG-nitro-L-arginine methyl ester, a nitric oxide synthase inhibitor (3 mg/kg; i.v.), significantly abolished the protective effect of GLP-1 on reserpine-induced gastric mucosal lesions (p<0.001, p<0.01 and p<0.01, respectively). CONCLUSIONS: We conclude that the sympathetic pathway, somatostatin and nitric oxide, but not the cholinergic pathway, contribute to the gastroprotective effect of intra-cerebroventricular GLP-1 on reserpine-induced gastric mucosal lesions.

Arginine vasopressin does not contribute to seizures induced by intracerebroventricularly-injected pilocarpine.

Arginine vasopressin (AVP) has been shown to contribute to the production of seizures. Here, we aimed to investigate the effects of AVP on seizures induced by intracerebroventricular (i.c.v.) injection of pilocarpine. Rats were treated with 0.2-2.4 mg/5 microl pilocarpine intracerebroventricularly, to obtain the dose-response relationship for behavioural seizures. 2.4 mg/5 microl pilocarpine induced status epilepticus in all rats and 0. 2 mg/5 microl pilocarpine did not produce any sign of seizure in any of the rats. In the second step, AVP (0.01-1000 ng/2 microl; i.c.v.) was injected 5 min before i.c.v. injection of a low dose pilocarpine (0.4 mg/5 microl) and rats were observed for percentage of status epilepticus, status epilepticus latency and behavioural seizure scores. None of the applied doses of AVP had any significant effect on seizures induced by 0.4 mg/5 microl i.c.v. pilocarpine. Subcutaneous injection of 1000 ng AVP 1h before 0.4 mg i.c.v. pilocarpine also did not produce significant difference with respect to the 0.4 mg pilocarpine group. Finally, pretreatment with neither an AVP V(1) receptor antagonist (25, 125, 250 ng/5 microl; i.c.v.) nor an AVP V(2) receptor antagonist (25, 125, 250 ng/5 microl; i.c.v.) prevented status epilepticus, induced by 2.4 mg/5 microl i.c.v. pilocarpine. We conclude that AVP does not act as a convulsant agent in centrally-induced pilocarpine seizures.

Investigation of the mechanisms involved in the central effects of glucagon-like peptide-1 on ethanol-induced gastric mucosal lesions.

The aim of this study was to investigate the effects of intracerebroventricularly injected glucagon-like peptide-1 (GLP-1) on ethanol-induced gastric mucosal damage and to elucidate the mechanisms involved. Absolute ethanol was administered through an orogastric cannula 5 min before GLP-1 (1 microg/10 microl) injection. One hour later, the rats were decapitated, their stomachs were removed and scored for mucosal damage. GLP-1 inhibited the ethanol-induced gastric mucosal damage by 92%. Centrally injected atropine sulphate, a muscarinic receptor antagonist (5 microg/10 microl), prevented the gastroprotective effect of GLP-1, while mecamylamine, a nicotinic receptor antagonist (25 microg/10 microl), was ineffective. Peripherally injected atropine methyl nitrate (1 mg/kg) did not change the effect of GLP-1, but mecamylamine (5 mg/kg) blocked it. Cysteamine, a somatostatin depletor (280 mg/kg, s.c.), did not affect the protective activity of GLP-1, while inhibition of nitric oxide (NO) synthesis by L-NAME (3 mg/kg, i.v.) significantly abolished the protective effect of GLP-1 on ethanol-induced gastric mucosal lesions. We conclude that central muscarinic and peripheral nicotinic cholinergic receptors and NO, but not somatostatin, contribute to the protective effect of intracerebroventricularly injected GLP-1 on ethanol-induced gastric mucosal damage.

Effects of centrally injected GLP-1 in various experimental models of gastric mucosal damage.

Glucagon-like peptide-1 (GLP-1) is accepted to be a peptide involved in the central regulation of gastrointestinal function, but its potential gastroprotective effect is not clear. The aim of this study was to investigate whether intracerebroventricularly injected GLP-1 has protective effects on gastric mucosal lesions induced by several models, and if yes, whether these effects are due to the gastric antisecretory effect of the peptide. GLP-1 which was injected in three different doses (1, 10, 100 ng/10 microl; i.c.v.) to conscious rats prevented the mucosal lesions induced by reserpine and ethanol, but did not prevent the gastric mucosal lesions induced by pyloric ligation. In addition, 1 ng/10 microl dose of centrally injected GLP-1 inhibited gastric acid secretion in pylorus-ligated rats. As a result, we conclude that intracerebroventricularly injected GLP-1 may play a role in the prevention of gastric mucosal lesions induced by certain experimental models and this gastroprotective effect may be independent from its antisecretory effect.

Effects of intracerebroventricularly injected glucagon-like peptide-1 on cardiovascular parameters; role of central cholinergic system and vasopressin.

We aimed to investigate the effects of intracerebroventricularly (i.c.v.) injected glucagon-like peptide-1 (GLP-1) on blood pressure and heart rate, and whether central cholinergic system and vasopressinergic system play roles in these effects. Male Wistar albino rats were used throughout the experiments. Blood pressures and heart rates were observed before and for 30 min following drug injections. i.c.v. GLP-1 (100, 500 and 1000 ng/10 microl) caused a dose-dependent increase in both blood pressure and heart rate. Nicotinic receptor antagonist mecamylamine (25 microg/10 microl, i.c.v.) and muscarinic receptor antagonist atropine (5 microg/10 microl, i.c.v.) prevented the stimulating effect of GLP-1 on blood pressure. The effect of GLP-1 on heart rate was blocked only by mecamylamine. The V1 receptor antagonist of vasopressin (B-mercapto B, B-cyclopentamethylenepropionyl, O-Me-Tyr,Arg)-vasopressin (10 microg/kg), that was applied intraarterially, only prevented the effect of GLP-1 on blood pressure, but did not show any effect on heart rate. Our data indicate that i.c.v. GLP-1 increases blood pressure and heart rate, and stimulation of central nicotinic and partially muscarinic receptors and vasopressinergic system play a role in the effects of i.c.v. GLP-1 on blood pressure. The effect of GLP-1 on heart rate may be partially due to stimulation of central nicotinic receptors.