Dataset Information

Effect of the nitric oxide donor, glyceryl trinitrate, on human gall bladder motility.

ABSTRACT: BACKGROUND: Nitric oxide is a major neurotransmitter in non-adrenergic, non-cholinergic (NANC) pathways. NANC inhibitory innervation has been shown in human gall bladder muscle in vitro; the role of nitric oxide in human gall bladder emptying however is undefined. AIMS: To study the effect of glyceryl trinitrate, a nitric oxide donor, on gall bladder emptying in healthy subjects using a randomised, double blind, cross-over, placebo controlled design. METHODS: Ultrasonographic gall bladder volume was measured in the fasting state in eight healthy volunteers after randomised administration of either glyceryl trinitrate 1200 micrograms buccal spray or placebo spray. On two further occasions, after randomised administration of either glyceryl trinitrate 1200 micrograms buccal spray or placebo spray, gall bladder volumes were also measured after a liquid test meal. RESULTS: Glyceryl trinitrate significantly increased fasting gall bladder volume to a mean of 114% (SEM 5%) of pretreatment volume (p = 0.039). Glyceryl trinitrate also significantly impaired gall bladder emptying between five and 40 minutes postprandially. Gall bladder ejection fraction was also reduced after glyceryl trinitrate compared with placebo (43 (6.9)% versus 68.4 (6.5)%, p = 0.016). CONCLUSIONS: This study shows that glyceryl trinitrate produces gall bladder dilatation in the fasting state and reduces postprandial gall bladder emptying, suggesting that nitric oxide mechanisms may be operative in the human gall bladder in vivo.

SUBMITTER: Greaves R

PROVIDER: S-EPMC1727023 | biostudies-other | 1998 Mar

REPOSITORIES: biostudies-other

ACCESS DATA

Similar Datasets

Project description:A Phase I, double-blind, randomized, crossover study in healthy males (N=106) was conducted between March 21, 2004, and May 17, 2004, to determine the magnitude and duration of the hemodynamic interaction of avanafil (a phosphodiesterase type-5 inhibitor for treating males with erectile dysfunction) when coadministered with glyceryl trinitrate (NTG) compared with sildenafil and placebo. Subjects received avanafil (200 mg), sildenafil (100 mg), and placebo (on separate days) via the oral route followed by NTG (0.4 mg) 12, 8, 4, 1, or 0.5 hours post-dose via the sublingual route. Blood pressure (BP) and heart rate (HR) were assessed at defined intervals. Throughout the study (after administration of the study drug, and including the period after NTG administration), the effects of avanafil and sildenafil on BP and HR were significantly greatest overall, at the shortest (0.5-hour) time interval compared with placebo. By the 8- and 12-hour time intervals, no significant difference in BP or HR was observed for avanafil (8 and 12 hours) or sildenafil (12 hours) (p>0.05, compared with placebo). Compared with avanafil, sildenafil had a significantly greater effect when dosed 0.5 hours before NTG on standing HR (p=0.05); 1 hour before NTG on standing systolic blood pressure (SBP) (p<0.05), sitting SBP (p=0.01) and standing HR (p<0.01); and 12 hours before NTG on standing SBP (p=0.05). Throughout the study, symptomatic hypotension adverse events occurred in 27%, 29%, and 12%, and clinically significant reductions in standing SBP (?30 mmHg) occurred in 15%, 29%, and 12% of subjects dosed with avanafil, sildenafil, and placebo, respectively (overall treatment differences: p<0.01 and p<0.05, respectively). These data show that avanafil and sildenafil have no significant effect on BP and HR if administered to healthy males ?8 hours (avanafil) or ?12 hours (sildenafil) before a sublingual dose of NTG. However, results may differ in populations with known vascular disease, especially those using other concurrent pharmacotherapy. These findings may be of interest to clinicians who treat patients with erectile dysfunction and who also have a cardiovascular condition. Of note, the applicability of these results in such patients may be limited because the enrollment comprised healthy, normal subjects.

Project description:BACKGROUND: Endoscopic sphincterotomy has been shown to inhibit stone formation in the gall bladder of experimental animals. AIMS: To investigate the alterations in bile composition and gall bladder motility after endoscopic sphincterotomy. PATIENTS: A study was performed of gall bladder bile composition and gall bladder motility in patients with gallstone disease ((n = 20; age 40-60 years, median age 55 years: seven men), with gall bladder calculi (n = 12) and with diseased gall bladder (chronic inflammation) without gall bladder calculi (n = 8)), who had received endoscopic sphincterotomy for common bile duct stones. Age and sex matched disease controls comprised 20 patients with gallstone disease but without stones and an intact sphincter of Oddi (with gall bladder calculi (n = 10) and diseased gall bladder without gall bladder calculi (n = 10)). METHODS: Gall bladder motility was assessed by ultrasound. Duodenal bile collected by nasoduodenal tube after stimulation of gall bladder by intravenous ceruletid infusion was analysed for cholesterol, phospholipid, and bile acid concentrations, cholesterol saturation index, and nucleation time. RESULTS: There was a significant reduction in mean (SEM) fasting volume (12.5 (1.7) ml v 26.4 (2.5) ml; p < 0.001) and mean (SEM) residual volume (4.34 (0.9) ml v 14.7 (0.98) ml; p < 0.001), and increase in mean (SEM) ejection fraction (65.7 (4.2)% v 43.6 (5.52)%; p < 0.001) and mean (SEM) rate constant of gall bladder emptying (-0.031/min v -0.020/min; p < 0.01) in patients who had been subjected to endoscopic sphincterotomy. Median nucleation time was significantly longer (17 days v 6 days; p < 0.006) in treated patients. There was a reduction in total mean (SEM) lipid concentrations (6.73 (0.32) g/dl v 7.72 (0.84) g/dl; p < 0.05), cholesterol (5.6 (1.5) mmol/l v 10.3 (2.23) mmol/l; p < 0.001) and CSI (0.72 (0.15) v 1.32 (0.31); p < 0.001). There was no significant change in mean (SEM) phospholipid (25.6 (3.5) mmol/l v 23.4 (6.28) mmol/l) and bile acid (93.7 (7.31) mmol/l v 105.07 (16.6) mmol/l) concentrations. CONCLUSIONS: After endoscopic sphincterotomy there was enhanced contractility of the gall bladder, accompanied by a prolongation of nucleation time and reduction in cholesterol saturation index.

Dataset Information

Effect of the nitric oxide donor, glyceryl trinitrate, on human gall bladder motility.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets