Mustafa Deniz

Mediators of glucagon-like peptide 2-induced blood flow: Responses in different vascular sites ☆

The aims of the present study were: to characterize the mechanisms of hemodynamic alterations induced by GLP-2, and, to compare the responses elicited in the superior mesenteric artery (SMA) to other vascular beds. Anesthetized rats were infused at the doses of 0.9, 2.3, 4.6 and 9.3 nmol/kg into the jugular vein for 60 min. Blood flow in the various arteries was measured by the ultrasonic transit time technique. Some animals were pretreated with indomethacin (5 mg/kg, ip), L-NAME (9, 18, 36 and 72 micromol/kg, iv), atropine sulfate (1-2 mg/kg, iv), CCK-1 and CCK-2 receptor antagonists (L-364,718 and L-365,260, 1 mg/kg, iv), exendin (9-39) amide (35 nmol/kg, iv) and lidocaine (74 micromol/kg, iv) prior to the infusion of GLP-2 (4.6 nmol/kg). In another group, capsaicin was applied either systematically (125 mg/kg, sc) or vagally (1 mg/rat). GLP-2 administration at all doses significantly increased the SMA blood flow throughout the experiments. GLP-2 (4.6 nmol/kg) infusion significantly increased blood flow of inferior mesenteric artery and carotid artery but not in any other vessel measured. Only the pretreatments with L-NAME and lidocaine were ineffective in preventing the GLP-2-induced responses. These results implicate that GLP-2-induced blood flow alterations are most significant in the SMA and are not mediated by prostaglandins, muscarinic, GLP-1 or CCK receptors. Our results also suggest that the stimulatory effect of GLP-2 on SMA blood flow is NO-dependent and mediated via intrinsic, non-cholinergic enteric neurons.

Blood flow alterations in TNBS-induced colitis: Role of endothelin receptors

AbstractObjectives:The aim of the present study was to investigate the time dependent changes in hemodynamic parameters and to assess the role of endothelin (ET) receptors in trinitrobenzene sulfonic acid (TNBS) induced colitis. Materials:Inferior mesenteric artery (IMA) hemodynamics, myeloperoxidase activity (MPO) and damage scores were measured immediately or 1, 3, 5 and 14 days after colitis. Treatments: Another group of rats received a nonselective ET receptor antagonist bosentan (30 mg/kg/day), ET-A receptor antagonist BQ485 (60 μg/rat/day) or ET-B receptor antagonist BQ788 (60 μg/rat/day) prior to and on the 1st, 2nd and 3rd days after TNBS administration. Results:IMA flow significantly increased at 90 min followed by a substantial decrease through days 1–5. Tissue MPO activity and macroscopic damage score increased on 1st day after the induction of colitis and remained elevated 3, 5 and 14 days following colitis. Treatment with bosentan or ET-A receptor antagonist largely prevented the colitis-induced reduction in blood flow and tissue injury whereas ET-B receptor antagonist did not attenuate tissue injury or reductions in blood flow. Conclusions:Our results demonstrate that time-dependent abnormalities occur in IMA hemodynamics following TNBS administration. Our findings also indicate that ET-A receptors but not ET-B receptors play an important role in the colonic inflammation following TNBS administration.

Cefaclor, a cephalosporin antibiotic, delays gastric emptying rate by a CCK-A receptor-mediated mechanism in the rat

Studies in vitro suggest that cephalosporin antibiotics release the gut hormone cholecystokinin. Cholecystokinin is known to inhibit gastric emptying. Here we examine the effects of cefaclor on gastric emptying and intestinal motility. Male Sprague‐Dawley rats were fitted with gastric cannulas. Following a 3‐week recovery, the rate of gastric emptying of saline, peptone (4.5%) or cefaclor was determined after instillation into the gastric cannula, while intestinal transit was measured by using the propagation of arabic gum + charcoal mixture given intraduodenally. Gastric emptying of saline was significantly delayed by the addition of cefaclor (3, 10, 30 or 100 mM). The CCK‐A antagonist SR‐27897B (1 mg kg−1, i.p.) reversed the delay induced by 10 mM cefaclor, whereas the CCK‐B antagonist CI‐988 (1 mg kg−1, i.p.) had no significant effect. In capsaicin‐treated rats, 10 mM cefaclor emptied more rapidly than in vehicle‐treated animals. Thirty‐minute intestinal transit was increased at 30 and 100 mM of cefaclor, while the gastric acid secretion following cefaclor instillation was no different than the group which received saline. The cephalosporin antibiotic cefaclor appears to be a potent stimulant of CCK release from gut endocrine cells, resembling the effects of peptone. Cefaclor delays gastric emptying via capsaicin‐sensitive afferent pathways, which involve CCK‐A receptor interaction.

Effect of sex steroids on colonic distension-induced delay of gastric emptying in rats

Background and Aim:  The objective of the present study was to examine the effect of gonadal hormones on gastric motor response to non‐noxious and noxious stimuli of colonic distension.

The Preventive Effect of Dopamine Infusion in Rats with Abdominal Compartment Syndrome

ABSTRACT Background: The most significant perfusion disorder of the intra-abdominal viscera occurs in the abdominal compartment syndrome (ACS). Free oxygen radicals diffuse into the body during the reperfusion phase of ACS. Our aim was to determine the effects of dopamine infusion (3 μg/kg/min) on renal perfusion, cytokine levels, free oxygen radicals, and renal histopathological changes in the presence of ACS in a prospective randomized manner. Methods: Twenty-four male Sprague-Dawley rats were randomly divided into four groups (n = 6). Group 1 was used as control. In group 2, air was inflated until the intra-abdominal pressure (IAP) reached 20 mmHg. In group 3, dopamine was infused for 60 min meanwhile IAP was kept at 20 mmHg. In group 4, dopamine was infused for 60 min before IAP rise. After this phase, renal artery (RA) perfusion was measured continuously. Myeloperoxidase activity (MPO), glutathione (GSH), and lipid peroxidation (MDA) levels were measured in tissue samples and histopathological scoring was performed. Results: Dopamine treatment before and during ACS significantly decreased MPO and MDA levels and also increased renal blood flow and GSH levels. However, histopathological damage was improved simultaneously. Conclusion: Dopamine infusion before and during ACS, increases renal perfusion and decreases free oxygen radicals. According to our findings, dopamine infusion may be proposed for the treatment of ACS and perfusion disorders in critically ill patients.

Nicotine withdrawal alleviates acetic acid-induced gastric injury in rats.

Epidemiological and experimental studies have demonstrated that cigarette smoking intensifies gastric ulceration. Although nicotine can act as an anxiolytic and antidepressant, its withdrawal may also lead to increased anxiety and depression. In order to associate the toxic actions of nicotine on gastric mucosa with alterations of anxiety level and to evaluate the impact of nicotine withdrawal on the anxiety level and the severity of ulcer, an acetic acid-induced ulcer model was used. Male Sprague-Dawley rats were given either tap water or nicotine bitartarate (50μg/ml in drinking water) for 15 days, while another group of rats had 5 days of withdrawal following 10 days of nicotine treatment. Ulcer was induced by acetic acid on the 15th day of the treatments, and the rats were followed for 3 days until they were decapitated and the gastric tissues were obtained. Using the hole-board test, basal anxiety levels measured on the first day of the treatments were compared with the measurements made at the early and late phases of ulcer induction. Chronic administration of nicotine did not have a potentiating effect on acetic acid-induced gastric ulcer, since the gastric injury, as assessed by both macroscopic and microscopic evaluation and increased gastric myeloperoxidase activity indicating neutrophil recruitment, was not exaggerated or attenuated by nicotine intake. On the other hand, nicotine withdrawal attenuated gastric mucosal injury, despite an increased level of anxiety. Smoking cessation, which triggers the onset of depressive symptoms with nicotine withdrawal, still has a worthwhile positive effect on the gastric mucosa.