Chris R . Triggle

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1. Vasorelaxant properties of three nitric oxide (NO) donor drugs (glyceryl trinitrate, sodium nitroprusside and spermine NONOate) in mouse aorta (phenylephrine pre-contracted) were compared with those of endothelium-derived NO (generated with acetylcholine), NO free radical (NO*; NO gas solution) and nitroxyl ion (NO(-); from Angeli's salt). 2. The soluble(More)
1. Endothelium-dependent and -independent regulation of vascular tone in small mesenteric arteries (SMA) from control (db/db +/?) and diabetic (db/db -/-) mice was compared. 2. Phenylephrine-induced maximum contraction, but not sensitivity, of SMA in db/db -/- compared to db/db +/? was enhanced. 3. Acetylcholine (ACh), but not sodium nitroprusside (SNP),(More)
BACKGROUND AND PURPOSE Endothelial dysfunction can be detected at an early stage in the development of diabetes-related microvascular disease and is associated with accelerated endothelial senescence and ageing. Hyperglycaemia-induced oxidative stress is a major contributing factor to the development of endothelial dysfunction. Clinical data indicate that(More)
Endothelium-derived hyperpolarizing factor (EDHF) is defined as the non-nitric oxide (NO) and non-prostacyclin (PGI2) substance that mediates endothelium-dependent hyperpolarization (EDH) of vascular smooth muscle cells (VSMC). Although both NO and PGI2 have been demonstrated to hyperpolarize VSMC by cGMP- and cAMP-dependent mechanisms, respectively, and in(More)
Robert Furchgott’s discovery of the obligatory role that the endothelium plays in the regulation of vascular tone has proved to be a major advance in terms of our understanding of the cellular basis of diabetic vascular disease. Endothelial dysfunction, as defined by a reduction in the vasodilatation response to an endothelium-dependent vasodilator (such as(More)
The contractile actions of the proteinase-activated receptor-2-activating peptides (PAR2APs), SLIGRL-NH2 (SL-NH2), SLIGKV-NH2 (KV-NH2), trans-cinnamoyl-LIGRLO-NH2 (tc-NH2), and the PAR1-AP. TFLLR-NH2 (TF-NH2) as well as trypsin and thrombin were studied in endothelium-denuded and intact human umbilical vein (HUV) ring preparations. In HUV rings with, but(More)
Hepatic gluconeogenesis is a main source of blood glucose during prolonged fasting and is orchestrated by endocrine and neural pathways. Here we show that the hepatocyte-secreted hormone fibroblast growth factor 21 (FGF21) induces fasting gluconeogenesis via the brain-liver axis. Prolonged fasting induces activation of the transcription factor peroxisome(More)
Postsynaptic alpha adrenoceptors have been characterized in rat superior mesenteric artery and branches of canine mesenteric artery. l-Phenylephrine, naphazoline and clonidine were used as agonists and prazosin and yohimbine were used as antagonists. The pA2 values for prazosin and yohimbine were determined against these agonists in canine and rat(More)
A peptide corresponding to a proteinase-activated receptor 2 (PAR(2))-activating peptide with an N-terminal furoyl group modification, 2-furoyl-LIGRLO-NH(2), was assessed for PAR(2)-dependent and -independent biological activities. 2-Furoyl-LIGRLO-NH(2) was equally effective to and 10 to 25 times more potent than SLIGRLNH(2) for increasing intracellular(More)
BACKGROUND AND PURPOSE Nitroxyl (HNO) is emerging as an important regulator of vascular tone as it is potentially produced endogenously and dilates conduit and resistance arteries. This study investigates the contribution of endogenous HNO to endothelium-dependent relaxation and hyperpolarization in resistance arteries. EXPERIMENTAL APPROACH Rat and mouse(More)