Histamine relaxation of aortic rings from diabetic rats

The effect of histamine-induced relaxation on thoracic aortic rings from rats 5, 12, 24 and 52 weeks following streptozotocin-induced diabetes was determined. Preliminary studies confirmed the dependence of histamine-induced relaxation and the independence of nitroglycerin-relaxation (GTN) on the presence of endothelium (EDRF). Diabetes was confirmed by blood glucose levels exceeding 300 mg/dl. Rings with endothelium were depolarized several times with 50 mM KCL and then contracted with phenylephrine (10^–6). Dose-response curves were plotted from data obtained following exposure to histamine (10^–7–10^–3) and GTN 10^–9–10^–7) and compared to responses from age-matched untreated controls, diabetic and diabetic rats treated with insulin (2 U/day).The relaxation produced by histamine on phenylephrine pre-contracted rings was similar in all three groups from 5-week age matched rats. However, histamine-induced relaxation from untreated diabetic rats was significantly depressed at 12, 24 and 52 weeks (p<0.001). Conversely there was no difference in the relaxation elicited by GTN on rings obtained from the three groups at any age. Pretreatment with diphenhydramine (5×10^–7) on aortic rings from 12 and 52-week age matched rats resulted in qualitatively similar histamine dose-response curves that were displaced about two orders of magnitude to the right, indicative of H₁ receptor competitive antagonism.These results demonstrate that the duration of diabetes alters the responsiveness of rat thoracic aortic rings to histamine but not to GTN and suggests that the responses elicited by certain agonists on target tissues may be significantly altered depending on the duration of diabetes.This study was supported by grants from the G. and L. Pfeiffer Medical Research Foundation, Veterans Administration and American Diabetes Association, Oregon Affiliate.     

Histamine metabolism in lungs of rats infected withNippostrongylus brasiliensis

Several parameters connected to histamine metabolism and mast cell number were examined in the lungs of rats infected with the nematodeNippostrongylus brasiliensis. Histamine levels as well as mast cell numbers were found to be increased on day 14 after infection and were elevated during the whole time of the experiment. Histidine decarboxylase activity also reached a peak on day 14. There was no measurable activity of diamine oxidase in the lungs of parasitized and normal rats. It is postulated that the increase in histidine decarboxylase activity and histamine concentration observed in the present study is related to the process of mastocytosis.     

Histamine metabolism and pinnal hyperaemia during magnesium deficiency in rats

The relation between histamine metabolism and an appearance of pinnal hyperaemia during magnesium (Mg) deficiency, and the effects of some factors on these were studied in 3-week-old Wistar rats. On a Mg-deficient diet (Mg 0.001%), the histamine concentrations in plasma and urine increased after 4-5 d, and reached a maximum after 6-12 d. Pinnal hyperaemia appeared during the same time course. The hyperaemia was reduced by the administration of antihistamines (cimetidine and diphenhydramine). These results indicate that pinnal hyperaemia during Mg deficiency is mediated by histamine. The administration of oestradiol benzoate (0.08 mg/100g body weight subcutaneously once a day for 8 d) and/or gamma-ray irradiation (600 rad/d before experiments) reduced the appearance of pinnal hyperaemia and the increment in the urinary histamine during Mg deficiency. The histamine content increased in the spleen and some tissues after 8 d, but not in the skin, with increasing the activity of histamine synthesis. The treatments mentioned above depressed the increment of histamine content. These results suggest that the pinnal hyperaemia and the increment of the urinary histamine in the Mg-deficient rat are related to the increment of both the histamine synthesis and release.     

Histamine uptake and metabolism in the blood vessels of rats

In vitro radiolabeled histamine uptake and metabolism were investigated in abdominal aorta, iliac artery, mesenteric artery and hepatic portal vein of the rat. Histamine uptake was rapid and remained linear over the initial 10 min of the accumulation period. The uptake rate was temperature sensitive with marked reduction in rate at 0°C. The accumulation at 0°C represents nonspecific uptake. The uptake of histamine was observed to be related to the amount of tissue stores of histamine as well as extracellular sodium ion concentration. The only histamine metabolite detected in the vasculature examined was imidazoleacetic acid representing almost 80% of the chromatogram radioactivity. This observation indicates the primary metabolic pathway for histamine in rat vasculature involves the enzyme, diamine oxidase.     

Histamine metabolism in asthma

Histamine and 1-methyl-imidazole-4-acetic acid, the end product of histamine metabolism via the ring-N methylation pathway, were measured in urine from asthmatic and nonasthmatic children on a histamine-restricted diet. No significant differences were found between the relative output values that could distinguish the asthmatic from the nonasthmatic children. The intermediary metabolite, methylhistamine, was also measured in some of these urine specimens, and no obvious differences were found between the proportions of the three substances that would suggest impairment of the methylation pathway of histamine metabolism in asthma.     

Histamine metabolism in the Arthus reaction

Histamine metabolism, i.e., concentration of histamine and activities of histamine-degrading enzymes, histamine-N-methyltransferase (HMT), and diamine oxidase (DAO), were examined in the Arthus reaction induced in guinea pig skin. The specific activity of HMT was 44.12 +/- 3.80 pmole/min/mg protein and was about 15 times greater than that of DAO in control specimens. However, HMT activity decreased time dependently to 35% of the control at 3 hr and to 10% 48 hr after the initiation of the reaction. DAO activity increased to 150% till 1 hr followed by a linear decrease to 35% at 6 hr and to 10% at 48 hr. Histamine concentration showed a prominent linear decrease to 15% of the control at 2 hr followed by an increase to about 85% at 6 hr. This biphasic change seemed to be well explained by the dynamic changes in the activities of histamine-degrading enzymes. Such decrease in enzyme activities were not observed in other experimentally induced inflammations including dinitrochlorobenzene allergic and croton oil dermatitis. The addition of tissue extract from the Arthus reaction sites resulted in about 30% inhibition in both of two enzyme activities, suggesting the presence of some inhibitory factor(s) in the reaction sites.     

Perturbation of 11-eicosenoate metabolism in female diabetic rats

Considering the proposed preventive effect of nervonic acid on obesity- and diabetes-related coronary risk factors, the content of its precursors (oleic, 11-eicosenoic and 13-docosenoic acids) was measured in liver and plasma phospholipids and triglycerides, brain and spleen phospholipids, and adipose tissue lipids of fed or overnight fasted control and hereditarily diabetic Goto-Kakizaki female rats, as well as fed streptozotocin-induced diabetic female rats. In liver and brain phospholipids, the 11-eicosenoate/oleate ratio was significantly higher in diabetic rats than in control animals. Such was not the case in either spleen phospholipids or liver triglycerides and adipose tissue lipids. The increase in the liver phospholipid 11-eicosenoate/oleate ratio found in female diabetic rats represents a mirror image of the situation recently documented, in the same animal models of diabetes, in male rats. These contrasting findings may be relevant to the higher coronary heart disease risk prevailing in female, as compared to male, diabetic subjects.     

Collagen metabolism in the myocardium of normal and diabetic rats

Myocardial collagen and total protein synthesis were studied in normal, diabetic, and insulin-treated diabetic rats after a single intraperitoneal injection of L-[2,3-3H]proline as a radioisotopic precursor. The incorporation of tritiated proline into myocardial protein was regarded as a measure of total protein synthesis and the incorporation into hydroxyproline as indicative of myocardial collagen synthesis. Both total protein and collagen synthesis were found to be significantly lower in diabetic rats. This was associated with decreased degradation of both total protein and collagen in diabetic rats, as suggested by prolonged turnover times. Collagen content was also found to be increased in diabetic myocardium. Early insulin therapy with normalization of blood sugars in diabetic rats returned myocardial collagen metabolism to normal. This suggests that maintenance of euglycemia in diabetic rats is necessary to prevent abnormal myocardial collagen metabolism.     

Histamine metabolism is altered in nasal polyposis

Inflammation Research -     

控制血糖促进糖尿病大鼠心肌葡萄糖代谢

目的 观察控制血糖对2型糖尿病大鼠心肌能量代谢的影响.方法 18只SD雄性大鼠随机分为对照组(6只)、糖尿病组(6只)和治疗组(6只).采用高脂喂养及腹腔注射链脲佐菌素建立2型糖尿病大鼠模型,应用离体心脏Langendorf灌注,测定心肌葡萄糖氧化率;采用Western blot法检测心肌细胞GLUT4的表达.结果 糖尿病组大鼠心肌葡萄糖总氧化量较对照组减少(P相似文献   

Sorbitol metabolism in inner medullary collecting duct cells of diabetic rats

Intracellular accumulation of sorbitol, generated fromd-glucose via the aldose reductase pathway, is thought to play an important role in diabetic complications such as lens cataracts and neuropathy. In order to elucidate the effect of diabetes on the renal inner medulla, another sorbitol-rich tissue, male Wistar rats were treated with a single dose of streptozotocin (60 mg/kg body weight, i.p.). Six wecks later total inner medullary tissue (IM) or isolated inner medullary collecting duct (IMCD) cells were prepared. In diabetic IM tissue, sorbitol content was 1.8-fold higher than in control IM tissue (134±17 vs. 74±22 mol/g tissue protein). Sorbitol production in both normal and diabetic IMCD cells was strongly dependent on extracellulard-glucose concentration. In normal cells, for example, sorbitol production was 90±9 mol sorbitol/g protein x h at 45 mMd-glucose compared to 13±1 mol/g protein x h at 5 mM. At identicald-glucose concentrations sorbitol synthesis in diabetic IMCD cells was, however, always significantly higher than in control cells (122% of control at 15 mM and 126% of control at 45 mM). In addition, aldose reductase activity in diabetic IM was found to be augmented. The maximal velocity was 4.2 times higher (97±22 U/g protein vs. 23±7 U/g protein) while theK _m of the enzyme remained unchanged. Membrane permeability for sorbitol or the response to changes in extracellular osmolarity was not significantly different in diabetic IMCD cells and normal cells with correspondingly high intracellular sorbitol concentrations. Similarly the kinetic parameters ofd-glucose uptake were not altered by streptozotocin treatment. These results suggest that increased medullary sorbitol content in diabetic rats is a result of increased sorbitol synthesis due to a higher extracellulard-glucose concentration and augmented aldose reductase activity in face of an unaltered sorbitol permeability of the plasma membrane.     

Histamine metabolism in patients with foregut carcinoid tumours

The urinary excretion of the histamine metabolite, tele-methylimidazoleacetic acid (MemAA), was measured in 15 patients with foregut carcinoid tumours (5 ECLomas, 4 gastric carcinoids of the mixed type and 6 bronchial carcinoids), High levels were related to tumour burden and presence of the foregut carcinoid syndrome. Control of symptoms was either achieved by octreotide in combination with blockade of histamine receptors or by hyperthermic liver perfusion chemotherapy. MemAA served as an exellent tumour marker for diagnosis and guidance of therapy.This work was supported by grants from the Swedish MRC (5520), Jubileumsklinikens Cancer Research Fund and Landstinget, Östergötland.     

Histamine uptake and metabolism in smooth muscle in vitro

Conclusion This evidence suggests that the histamine-releasing agent in hemp dust may act by a mechanism similar to that of compound 48/80.