Kasim Ozluk

Effects of intracerebroventricularly-injected morphine on anxiety, memory retrieval and locomotor activity in rats: involvement of vasopressinergic system and nitric oxide pathway.

Morphine has been shown to alter several behavioural processes. We aimed to investigate the effects of intracerebroventricular (i.c.v.) morphine on anxiety, memory retrieval and locomotor activity in rats and to elucidate the possible involvement of the vasopressinergic system and the nitric oxide (NO) pathway in these effects. Rats were pretreated with morphine (0.5, 5, 50 microg/5 microl; i.c.v.) or saline (5 microl; i.c.v.) 30 min before the elevated plus maze test, the probe trial of the Morris water maze and the open field test. Morphine (5 microg/5 microl; i.c.v.) induced significant anxiolytic effects in the elevated plus maze. None of the doses of morphine produced any effects in the probe trial of the Morris water maze and the open field. Pretreatment with an arginine vasopressin (AVP) V(1) receptor antagonist (25, 125 ng/5 microl; i.c.v.), an AVP V(2) receptor antagonist (25, 125 ng/5 microl; i.c.v.), or L-NAME, an NO synthase inhibitor (5, 25 microg/5 microl; i.c.v.) 30 min before morphine significantly prevented the anxiolytic effects of morphine. These results suggest that i.c.v. morphine has significant anxiolytic effects, probably mediated by both vasopressinergic system and NO pathway, but has no effect on memory retrieval or locomotor activity, at least at the applied doses.

Central injection of captopril inhibits the blood pressure response to intracerebroventricular choline

In the present study, we investigated the involvement of the brain renin-angiotensin system in the effects of central cholinergic stimulation on blood pressure in conscious, freely moving normotensive rats. In the first step, we determined the effects of intracerebroventricular (icv) choline (50, 100 and 150 microg) on blood pressure. Choline increased blood pressure in a dose-dependent manner. In order to investigate the effects of brain renin-angiotensin system blockade on blood pressure increase induced by choline (150 microg, icv), an angiotensin-converting enzyme inhibitor, captopril (25 and 50 microg, icv), was administered 3 min before choline. Twenty-five microg captopril did not block the pressor effect of choline, while 50 microg captopril blocked it significantly. Our results suggest that the central renin-angiotensin system may participate in the increase in blood pressure induced by icv choline in normotensive rats.

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.

Cardiovascular effects of the intracerebroventricular injection of adrenomedullin: roles of the peripheral vasopressin and central cholinergic systems

Our objective was to investigate in conscious Sprague-Dawley (6-8 weeks, 250-300 g) female rats (N = 7 in each group) the effects of intracerebroventricularly (icv) injected adrenomedullin (ADM) on blood pressure and heart rate (HR), and to determine if ADM and calcitonin gene-related peptide (CGRP) receptors, peripheral V1 receptors or the central cholinergic system play roles in these cardiovascular effects. Blood pressure and HR were observed before and for 30 min following drug injections. The following results were obtained: 1) icv ADM (750 ng/10 µL) caused an increase in both blood pressure and HR (ΔMAP = 11.8 ± 2.3 mmHg and ΔHR = 39.7 ± 4.8 bpm). 2) Pretreatment with a CGRP receptor antagonist (CGRP8-37) and ADM receptor antagonist (ADM22-52) blocked the effect of central ADM on blood pressure and HR. 3) The nicotinic receptor antagonist mecamylamine (25 µg/10 µL, icv) and the muscarinic receptor antagonist atropine (5 µg/10 µL, icv) prevented the stimulating effect of ADM on blood pressure. The effect of ADM on HR was blocked only by atropine (5 µg/10 µL, icv). 4) The V1 receptor antagonist [β-mercapto-β-β-cyclopentamethylenepropionyl1, O-me-Tyr2,Arg8]-vasopressin (V2255; 10 µg/kg), that was applied intravenously, prevented the effect of ADM on blood pressure and HR. This is the first study reporting the role of specific ADM and CGRP receptors, especially the role of nicotinic and muscarinic central cholinergic receptors and the role of peripheral V1 receptors in the increasing effects of icv ADM on blood pressure and HR.

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.

An anatomical and pathological evaluation of middle cerebral artery occlusion in rats.

Abstract Adult male Sprague-Dawley rats (n = 87) weighing 350-400 g were used for studying the anatomy of the horizontal segment of middle cerebral artery and infarct area after occlusion of the artery. In the experimental group (n = 27) middle cerebral artery was coagulated 3-4 mm length from the origin of the lateral striate arteries to the inferior cerebral vein and divided. Control rats (n = 20) had all the surgical procedures except occlusion. Another group of rats (n = 40) were used to determine the anatomical variations of middle cerebral artery after intracarotid carbon black injection. Five major patterns of middle cerebral artery were observed and two of them were major and constituted 92.5% of rats. Twenty-four hours after middle cerebral artery occlusion, all animals were neurologically evaluated. On the third day after occlusion the brains were stained with 2% 2,3,5-triphenyltetrozolium chloride. The area of Infarction was assessed by computerized analysis method. In our study after determining the variations of the middle cerebral artery and Its branches in our strain of rats, we were able to achieve 92.5% grade III and IV infarcted area. [Neurol Res 2000; 22: 609-614]

Chlorogenic Acid Enhances Abdominal Skin Flap Survival Based on Epigastric Artery in Nondiabetic and Diabetic Rats.

AbstractPrevious studies showed that chlorogenic acid (CGA) accelerates wound healing via its antioxidant activity. We aimed to investigate the effect of CGA in an experimental epigastric abdominal skin flap model in nondiabetic and diabetic rats. Rats were firstly divided into 2 groups: nondiabetic and diabetic. Diabetes was induced by streptozotocin. Then, 4 subgroups were created for each group: vehicle as well as 0.2 mg/0.5 mL, 1 mg/0.5 mL, and 5 mg/0.5 mL CGA treatments. Right epigastric artery–based abdominal skin flaps were elevated and sutured back into their original position. Chlorogenic acid or vehicle was injected once into the femoral arteries by leaving the epigastric artery as the single artery feeding the flaps during the injection. On postoperative day 7, flap survivals were evaluated, and the rats were killed. Distal flap tissues were collected for histopathological and biochemical assays. Chlorogenic acid showed greater flap survival in both nondiabetic and diabetic rats. Capillary density was increased, and necrosis was reduced in the CGA-treated rats. Chlorogenic acid decreased malondialdehyde levels as well as increased reduced glutathione and superoxide dismutase levels in the flap tissues. This study showed that CGA significantly improved flap survival by its antioxidant activities with intra-arterial local injections.

A central link between angiotensinergic and cholinergic systems; role of vasopressin.

Participation of central cholinergic system in the effects of intracerebroventricular (i.c.v.) injection of angiotensin II (Ang II) on blood pressure and heart rate was studied in conscious, freely moving rats. Ang II dose-dependently increased blood pressure and decreased heart rate. Both atropine and mecamylamine (i.c.v.) pretreatments prevented the cardiovascular effects of Ang II. Pretreatment with a vasopressin V1 antagonist also prevented the cardiovascular responses to Ang II. Our data suggest that the central pressor effect of Ang II is mediated in part by central acetylcholine via both muscarinic and nicotinic receptors, and vasopressin participates in this effect through V1 receptors.

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

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

1 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. 2 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. 3 Intracerebroventricular (i.c.v.) injection of choline (12.5–150 µg), 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 µg, increased blood pressure. 4 Intraperitoneal (i.p.) administration of 150 µg 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 µg, i.c.v.), ACh (10 µg, i.c.v.), carbamylcholine (10 µg, i.c.v.) and cytidine 5′‐diphosphocholine (CDP‐choline; 250 µg, i.c.v.) increased blood pressure and attenuated plasma renin responses to graded haemorrhage. 5 Inhibition of PRA by i.c.v. choline was abolished by i.c.v. pretreatment with mecamylamine (50 µg), but not atropine (10 µg). Blood pressure responses to choline (150 µg) were attenuated by pretreatment with both mecamylamine and atropine. 6 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. 7 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.