Effect of the angiotensin-converting enzyme inhibitor imidapril on reactive hyperemia in patients with essential hypertension: relationship between treatment periods and resistance artery endothelial function

AbstractOBJECTIVESThe purpose of this study was to evaluate the effects of the angiotensin-converting enzyme (ACE) inhibitor imidapril and the calcium antagonist amlodipine on endothelial function before and after 2, 4, 8, 12, 24 and 48 weeks of treatment.BACKGROUNDThere are limited data on whether and how long endothelial function is improved after initiation of ACE inhibitor treatment and how the grade of endothelial function further progresses after improvement of endothelial dysfunction in patients with essential hypertension.METHODSThe forearm blood flow (FBF) was measured in 25 patients with essential hypertension and in 25 normotensive subjects by using strain-gauge plethysmography during reactive hyperemia (RH) (280 mm Hg for 5 min) and after sublingual administration of nitroglycerin (NTG, 0.3 mg).RESULTSThe FBF of patients with essential hypertension during RH was significantly less than that of normotensive subjects. The increase in FBF after sublingual NTG was similar in both groups. Both imidapril (n = 13) and amlodipine (n = 12) significantly reduced systolic blood pressure and diastolic after eight weeks of treatment from the pretreatment values. Forearm vascular resistance was significantly decreased after two weeks of treatment. Imidapril significantly augmented RH after 12 weeks of treatment from the pretreatment values (31.6 ± 5.7 to 38.2 ± 6.0 ml/min per 100 ml tissue, p < 0.05), whereas amlodipine did not alter RH for each treatment period. The ability of imidapril to improve RH was maintained throughout the 48-week treatment period. There was no significant difference in RH at 12, 24 and 48 weeks. The increase in FBF after sublingual administration of NTG was similar in all treatment periods for the two groups. The infusion of NG-monomethyl-L-arginine, a nitric oxide (NO) synthase inhibitor, abolished the enhancement of RH in hypertensive patients treated with imidapril.CONCLUSIONSThese findings suggest that the ACE inhibitor imidapril augments RH after 12 weeks of treatment in patients with essential hypertension and that this ACE inhibitor-induced augmentation of RH may be due to an increase in NO

Flow-mediated vasodilation of human epicardial coronary arteries: effect of inhibition of nitric oxide synthesis

AbstractObjectives. This study sought to investigate the role of nitric oxide, an endothelium-derived relaxing factor, in flow-mediated vasodilation in human epicardial coronary arteries.Background. Endothelium-derived relaxing factors may be released from the coronary artery endothelium in response to increases in blood flow.Methods. We studied the effect of the nitric oxide synthesis inhibitor NG-monomethyl-l-arginine (l-NMMA) on the flow-mediated vasodilation of epicardial coronary arteries in 12 patients, using quantitative angiographic and Doppler flow velocity measurements. Adenosine at 100 μg/min was infused into the left anterior descending coronary artery to test the dilator response of the proximal artery to increases in blood flow. Acetylcholine at 3 and 30 μg/min was infused into the left coronary ostium to determine endothelium-dependent vasodilation of the proximal left anterior descending artery. Adenosine and acetykholine were infused before and after the intracoronary infusion ofl-NMMA (25 μg/min for 5 min).Results. Infusion ofl-NMMA caused a significant decrease in the baseline diameter of the proximal left anterior descending artery (from 2.90 ± 0.14 to 2.74 ± 0.13 mm [mean ± SEM], p < 0.01). Adenosine increased coronary blood flow Wore and afterl-NMMA (+3995 ± 27.5% and +511.9 ± 33.3%, respectively). Flow-mediated vasodilation was observed in the proximal left anterior descending artery before and afterl-NMMA (+9.2 ± 1.5%, p < 0.01 and +8.6 ± 2.1%, p < 0.01, respectively). A dose of 3 μg/min of acetylcholine significantly dilated the proximal left anterior descending artery beforel-NMMA (+7.6 ± 1.0%, p < 0.01), but acetylcholine-induced vasodilation was attenuated afterl-NMMA (−1.8 ± 1.0%).Conclusions. Our data suggest that nitric oxide modulates basal coronary artery tone but that mediators other than nitric oxide may be responsible for the flow-mediated vasodilation of human epicardial coronary arteries

Cholecystokinin receptor antagonist, loxiglumide, inhibits invasiveness of human pancreatic cancer cell lines

AbstractRecently, cholecystokinin has been reported to be important in regulating the growth of pancreatic cancer. We investigated the effect of loxiglumide (LXG), a cholecytskinin receptor antagonist, on the invasiveness of two human pancreatic cancer cell lines. Cells were treated with LXG for 24 h, and examined in the invasion assay. The expression and activity of MMP-9 in supernatants from cancer cells were analyzed by Western blotting and zymogram. Interestingly, the invasiveness of cancer cells and expression of MMP-9 were decreased by LXG in a dose-dependent manner. LXG may be a useful therapeutic agent against pancreatic cancer

Distribution and Endocrine Morphology of Polypeptide YY (PYY) Containing Cells in the Human Gut

Using human materials, the distribution of PYY containing cells was determined by immunocytochemical methods and discussion was made on their morphological endocrinology. PYY cells were fairly numerous in the lower gastrointestinal tract of man, particularly in the colon and rectum. The cells were also present in the pancreas and duodenum but quite rarely. PYY cells were not observed at all in the lower part of the esophagus, stomach and gall bladder. Their peculiar and characteristic shapes as well as distribution suggest that PYY may have some action (probably specific) on the function of the distal gastrointestinal tract

Transient Regional Wall Motion Abnormality and Increased Wall Thickness of the Left Ventricle in Acute Myopericarditis Occurring in the Puerperium

An unusual sequence of echocardiographic abnormalities of a 25-year-old female with acute myopericarditis was described. She presented with shortness of breath and a high body temperature after the birth of her first child. Regional asynergy and increased thickness of the left ventricle were transiently observed by echocardiography. It is considered that these abnormalities resulted from inflammatory changes in heart muscle such as edema, which was ascribable to acute myopericarditis in the puerperium

A Galanin-Like Peptide in the Colon of the Golden Hamster

Galanin-like immunoreactive peptide was studied in the colonic wall of the golden hamster using the immunoflurescent technique. Galanin-like immunoreactivity was observed mainly in cell bodies of the myenteric plexus and in fibers in the lamina propria mucosae and in the circular muscle layer. The submucosal plexus and submucosal connective tissue, however, contained very little galanin-like immunoreactive peptide. This peptide appears to be instrinsic mainly to the colon. The presence of the peptide indicates some possible biological roles in the colonic function

Endocrine Profile in Rats with Postgastrectomy Malabsorption: a Pilot Study

Abnormal endocrine profile, especially in the enteropancreatic axis, was described in rats with malnutrition caused by malabsorption after total gastrectomy. Insulin, substance P and motilin concentrations at the fasting condition were significantly elevated in malnutritious rats after total gastrectomy when compared to those in control rats. A significant elevation of pancreatic glucagon and motilin was noted after intraduodenal fat administration in malnutritious rats. These data suggest that these peptides of many humoral factors may thus cause abnormal enteropancreatic axis and consequent malnutrition

Preventive Effect of Proglumide on Erosive Gastritis in the Rat

The purpose of this study is to determine whether or not proglumide has a preventive effect on the erosive gastritis induced by sodium salt of taurocholic acid (TCA) in the rat. Its effect on the formation of gastric erosions, serum gastrin levels and secretion of acid and pepsin were also studied. The rats were given standard feed containing 0.25% proglumide and water containing 5mM TCA (experimental E group). The control rats were given standard feed and water containing 5mM TCA (TCA group). All rats were killed at the end of the 3 months. The tissue specimens of the resected gastric mucosa were stained with hematoxylin eosin for histopathology and with azan for evaluation of fibrous ploriferation. From microscopic observation of the stained specimens, the following results were obtained. TCA-group showed long mucosal surface injury (erosion), inflammatory cell infiltration, a reduction in the number of parietal cells, a decrease of mucosal thickness, and proliferation of collagenous fiber. In contrast, in the E group, these morphological and morphoquantitative changes were significantly small. The length of erosion and inflammatory cell infiltration were significantly reduced in the E group when compared with the TCA group. Furthermore, mucosal thickness was almost normal and fibrous proliferation was significantly scarce in the E group. Proglumide had an insignificant effect on pH on the mucosa, volume and pH of gastric juice, serum gastrin levels and tetragastrin-induced secretion of acid and pepsin. It is, thus, evident that proglumide has a preventive effect on the induction of erosive gastritis caused by TCA in the rats. Since it is difficult to explain its mechanism for the prevention of gastritis from only the already known facts that it has protective action on gastric mucosa and an inhibitory effect on secretion of acid and pepsin, unknown mechanisms are suspected to be involved

Induction of Experimental Atrophic Gastritis by N-Methyl-N'-Nitro-N-Nitrosoguanidine or Taurocholic Acid in Donryu Rats

The morphology of the rat (Donryu) gastric mucosa was examined by light microscopy after administration of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) or taurocholic acid (TCA), a component of bile acids. MNNG was given to rats ad libitum from light-sealed bottles for 5 months and deionized water was given freely for 6 months thereafter. TCA was administered to rats freely for 11 months. Deionized water was given to rats as control (non-treated rats). Rats treated with MNNG or TCA and control rats were killed at 11 months after the beginning of the experiment. Using 3 micron tissue samples taken from the area of the gastric mucosa designated before the experiment, hematoxylin and eosin and azan stain were made for histopathological evaluation and fibrosis. Marked atrophic changes, such as reduction in the number of parietal cells, shortened mucosa! length, inflammaotry cell infiltration, and proliferation of fibrosis, were present in the gastric mucosa of rats treated with MNNG as well as TCA. These findings were typical for atrophic gastritis. Such atrophic changes were slight in the gastric mucosa of the control rats. The frequency of tumourous lesions was very low in MNNG-treated rats. We have concluded on the basis of the present data that MNNG as well as TCA can induce atrophic gastritis in Donryu rats