Angiotensin II AT1Receptor Blockade Prevents Gastric Ulcers during Cold-Restraint Stress

Increased fecal pellet output that occurs during cold-restraint stress (CRS) was evaluated systematically. Free-feeding rats, which exhibit a reduced occurrence of gastric ulcers under these conditions, were studied. CRS significantly increased fecal pellet production and fluid content. However, the fecal output produced during CRS was not associated with increased gut secretory activity or somatic motor activity associated with cold restraint and did not occur in anesthetized animals. Cold and restraint stress were additive in producing increased fecal output. Significant dose-related decreases in fecal output were produced by drugs that decrease gut transit (i.e., B-HT 920, clonidine, Lomotil, loperamide, and lidamidine). Anticholinergic-antisecretory drugs, antidepressants, and tranquilizers had little effect on fecal output or fluid content. Changes in gastrointestinal transit did not contribute to the increased fecal output during CRS. Transit in the lower small intestine was not altered, but the cecum tended to empty more contents into the large intestine during CRS. Colonic transit was dramatically affected by CRS, which eliminated retrograde transit and produced the evacuation of the majority of colonic contents. The increased colonic transit produced by CRS was decreased in a dose-related fashion by hexamethonium, nifedipine, loperamide, and B-HT 920. In several time-response and drug-inhibition studies during CRS, both fecal pellet output and colonic transit were affected similarly. These data indicate that CRS appears to change central nervous system output to the colon and that it alters colonic smooth muscle motility in a manner that facilitates colonic transit and evacuation. Small intestinal transit is not involved in this phenomenon and is regulated differently during CRS.

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Anti-inflammatory effects of angiotensin II AT1 receptor antagonism prevent stress-induced gastric injury

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.00058.2003 ◽

2003 ◽

Vol 285 (2) ◽

pp. G414-G423 ◽

Cited By ~ 79

Author(s):

Claudia Bregonzio ◽

Ines Armando ◽

Hiromichi Ando ◽

Miroslava Jezova ◽

Gustavo Baiardi ◽

...

Keyword(s):

Blood Flow ◽

Angiotensin Ii ◽

Gastric Mucosa ◽

Restraint Stress ◽

Neutrophil Infiltration ◽

Gastric Blood Flow ◽

Gastric Injury ◽

Tnf Α ◽

Cold Restraint Stress ◽

Cold Restraint

Stress reduces gastric blood flow and produces acute gastric mucosal lesions. We studied the role of angiotensin II in gastric blood flow and gastric ulceration during stress. Spontaneously hypertensive rats were pretreated for 14 days with the AT1 receptor antagonist candesartan before cold-restraint stress. AT1 receptors were localized in the endothelium of arteries in the gastric mucosa and in all gastric layers. AT1 blockade increased gastric blood flow by 40–50%, prevented gastric ulcer formation by 70–80% after cold-restraint stress, reduced the increase in adrenomedullary epinephrine and tyrosine hydroxylase mRNA without preventing the stress-induced increase in adrenal corticosterone, decreased the stress-induced expression of TNF-α and that of the adhesion protein ICAM-1 in arterial endothelium, decreased the neutrophil infiltration in the gastric mucosa, and decreased the gastric content of PGE2. AT1 receptor blockers prevent stress-induced ulcerations by a combination of gastric blood flow protection, decreased sympathoadrenal activation, and anti-inflammatory effects (with reduction in TNF-α and ICAM-1 expression leading to reduced neutrophil infiltration) while maintaining the protective glucocorticoid effects and PGE2 release. Angiotensin II has a crucial role, through stimulation of AT1 receptors, in the production and progression of stress-induced gastric injury, and AT1 receptor antagonists could be of therapeutic benefit.

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Antioxidant Capacity, Cytoprotection, and Healing Actions of the Leaf Aqueous Extract of Ocimum suave in Rats Subjected to Chronic and Cold-Restraint Stress Ulcers

Ulcers ◽

10.1155/2013/150780 ◽

2013 ◽

Vol 2013 ◽

pp. 1-9 ◽

Cited By ~ 2

Author(s):

Paul V. Tan ◽

C. Mezui ◽

G. E. Enow-Orock ◽

G. Agbor

Keyword(s):

Antioxidant Capacity ◽

Restraint Stress ◽

Gastric Ulcers ◽

Control Group ◽

Stress Ulcers ◽

Mucus Production ◽

Cold Restraint Stress ◽

Cold Restraint ◽

Restraint Stress Ulcers

We evaluated the qualitative chemical composition and tested the antiulcer actions on cold/restraint stress ulcers, the healing effect on chronic acetic acid-induced gastric ulcers, and the in vivo and in vitro antioxidant capacity of Ocimum suave extract. Triterpenes, flavonoids, sugars, phenols, sterols, and multiple bonds were among the phytochemicals detected. The extract (250–500 mg/kg) dose-dependently inhibited the formation of gastric ulcers induced by cold/restraint stress (52.30%–83.10%). The prophylactic actions were associated with significant increases in gastric mucus production. There was significant histological healing of chronic ulcers following 14-day treatment with O. suave extract (250–500 mg/kg). We also evaluated the efficacy of O. suave extract in cold/restraint-induced oxidative stress in rat stomach tissue. O. suave (500 mg/kg) ameliorated the decreased levels of reduced glutathione from 0.85 (control group) to 2.08 nmol/g tissue. The levels of SOD and catalase were also improved in rats treated with O. suave extract. The extract had a high phenol content (899.87 mg phenol/g catechin equivalent), in vitro DPPH radical scavenging activity (89.29%), and FRAP (antioxidant capacity) (212.64 mg/g catechin equivalent). The cytoprotective and ulcer healing effects of the extract are attributed to enhanced mucus production and the antioxidant properties which may likely be associated with the high presence of flavonoids and polyphenols.

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Evaluation of Antiulcerogenic Activity of Clerodendron Infortunatum Extract on Albino Rat Gastric Ulceration

Journal of Drug Delivery and Therapeutics ◽

10.22270/jddt.v9i4-a.3337 ◽

2019 ◽

Vol 9 (4-A) ◽

pp. 57-62

Author(s):

Arun Kumar ◽

Rahul Shukla ◽

Anurag Chaudhary

Keyword(s):

Acetic Acid ◽

Gastric Ulcer ◽

Restraint Stress ◽

Ethanolic Extract ◽

North India ◽

Gastric Ulcers ◽

Albino Rat ◽

Pylorus Ligation ◽

Cold Restraint Stress ◽

Cold Restraint

Clerodendron infortunatum Linn. (Verbenaceae) is an important and widely used medicinal plant, reported to contain active bitter substance like clerodin, has been widely used as tonic and anthelmintic agent in the country sides of North India. Though, variously used in Ayurveda, Unani system of medicine and Homeopathy in case of ailments like diarrhoea, skin disorders, venereal and scrofulous complaints, wounds, post-natal complications, as vermifuge, laxative and cholagogue, for the removal of ascarids in anus, as external applications on tumours, etc., Background: The present study reports the antiulcer properties of 50% ethanolic extract of Clerodendron infortunatum Linn. (Verbenaceae) leaves have assessed in different acute and chronic gastric ulcer models in rats. Methods: EECI (100, 200 and 400 mg/kg body weight) was administered orally, twice daily for 5 days for prevention from ethanol (EtOH), Cold-restraint stress (CRS), Pylorus-ligation (PL) and 10 days for prevention of acetic acid induced ulcers. Results: The EECI showed significant gastric ulcer protective effect in doses of 400 mg/kg, when given twice daily for 5 days against gastric ulcers induced by ethanol (EtOH), cold restraint stress (CRS) and pyloric ligation (PL). EECI showed dose dependent decrease in ulcer index (UI) against ulcers induced by: (i) Ethanol (control UI: 29.52±2.4 mm2/rat, EECI decrease 21.12±2.3 – 5.3±1.0 (ii) Cold restraint stress (CRS) (control UI: 32.13±2.1, EECI decrease 24.02±2.2 – 4.7±1.1 (iii) pylorus ligation (control UI: 29.25±2.4 mm2/rat, EECI decrease 22.32±2.7 – 5.3±1.0, EECI 400 mg/kg significantly healed ulcers induced by 50% acetic acid after 5 (control UI: 32.30 ± 2.9, EECI decrease 26.27±1.9 – 8.56±0.98 and after 10 days treatment (control UI: 29.02 ± 2.6, healing 21.28±2.1 – 5.78±1.2. EECI prevents the oxidative damage of gastric mucosa by blocking lipid peroxidation and by significant decrease in superoxide dismutase, and increase in catalase activity. Conclusions: Our results show that Clerodendron infortunatum Linn. (Verbenaceae) possess significant gastro-protective activity which might be due to gastric defence factors and clerodin might be the main constituents responsible for this activity.

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