Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0009443 (cold)
 92,137 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Endothelin is a potent hepatic vasoconstrictor. We evaluated the role of an endothelin antagonist in hepatic ischemia/reperfusion injury. Bosentan, a novel endothelin receptor antagonist, was infused directly into the portal vein prior to cold ischemia and immediately on reperfusion, in five porcine livers. Five other pigs underwent routine liver harvest and reperfusion without bosentan treatment. Hepatic vascular resistance and liver tissue blood flow, as measured by thermistor flow probes, were determined following reperfusion. Hepatocellular damage was assessed through hepatic venous levels of sorbitol dehydrogenase and lactate dehydrogenase. Endothelial cell damage was determined in sections immuno-stained for factor VIII. Graft function was determined through oxygen consumption, bile production, and response to bile acid challenge. Organs treated with bosentan demonstrated lower vascular resistance and enhanced tissue blood flow (P < 0.05) as compared to untreated organs. Portal vein inflow to hepatic tissue was significantly enhanced (4.4-fold) in the bosentan-treated organs (P < 0.05). No difference was observed in hepatocellular damage. Pathology scores for factor VIII immunohistochemical staining were 2.3-fold higher in the bosentan-treated livers as compared to untreated livers (P < 0.05). The bosentan-treated livers also demonstrated enhanced oxygen consumption, increased bile production, and augmented biliary response to a bile acid challenge (P < 0.05). These results indicate that administration of bosentan before and after ischemia/reperfusion reduces hepatic circulatory disturbances, diminishes endothelial cell damage, and augments hepatic graft function.
 ...
PMID:Bosentan, an endothelin antagonist, augments hepatic graft function by reducing graft circulatory impairment following ischemia/reperfusion injury. 1136 57

Several maneuvers usually employed to set up isolated vascular preparations could effect the endothelium-dependent relaxation (EDR). The effects of five such maneuvers were studied in rings of rat aorta: 1) Type of anesthesia, 2) Cold storage of the vessels, 3) Length of the stabilization period, 4) Repeated contractions during stabilization, and 5) Performance of washouts during stabilization. Repeated contractions with norepinephrine (NE) 0.1 microM after stabilization altered neither the contraction nor the EDR induced by acetylcholine (Ach) 1 microM. Pentobarbital anesthesia and cold storage of the preparations for 24 h significantly decreased the EDR without effecting the contractile response of the rings. The absence of washouts during stabilization increased the contractions to either NE 0.1 microM or KCl 80 mM by nearly 50%. This increase was prevented by endothelial disruption or, in the presence of intact endothelium, by repeated washouts or by incubation with Bosentan 22 microM. It is concluded that 1) Anesthesia of the animals and cold storage of the preparations can alter the EDR even in the absence of contractile changes in the smooth muscle, and 2) Accumulation of endothelin during the incubation period, even if not producing changes in the resting tension, can substantially alter the subsequent response to vasoactive interventions.
 ...
PMID:Influence of several methodological procedures utilized to obtain in vitro vascular preparations on endothelial activity. 1182 75

The susceptibility of changes in responsiveness to noxious cold stimulation of rats submitted to chronic constriction of the infraorbital nerve (CION) or carrageenan to drug inhibition was compared. Nocifensive responses were measured as total time rats engaged in bilateral facial grooming with both forepaws over the first 2 min following tetrafluoroethane spray application to the snout. Carrageenan (50 microg, s.c. into upper lip) caused short-lived ipsilateral cold hyperalgesia (peak at 3 h: vehicle 8.4+/-1.3, carrageenan 21.2+/-3.0 s) which was markedly suppressed by i.p. indomethacin (4 mg/kg), celecoxib (10mg/kg) or s.c. dexamethasone (0.5 mg/kg), endothelin ET(A) or ET(B) receptor antagonists (BQ-123 and BQ-788, respectively; 10 nmol/lip). CION caused ipsilateral cold hyperalgesia between Days 2 and 12, which peaked on Days 4 (sham 15.3+/-1.8, CION 32.4+/-5.3s) to 6. Established peak CION-induced cold hyperalgesia was unaffected by indomethacin and celecoxib, whereas dexamethasone, BQ-123, BQ-788, and i.v. injections of selective antagonists of ET(A) (atrasentan, 3-10 mg/kg) or ET(B) (A-192621, 5-20 mg/kg) receptors caused significant inhibitions lasting 1-2.5h (peaks approximately 65-90%). Bosentan (dual ET(A)/ET(B) receptor antagonist, 10 mg/kg, i.v.) abolished CION-induced cold hyperalgesia for up to 6h. Thus, once established, CION-induced orofacial hyperalgesia to cold stimuli appears to lack an inflammatory component, but is alleviated by endothelin ET(A) and/or ET(B) receptor antagonists. If this CION injury model bears predictive value to trigeminal neuralgia (i.e., paroxysmal orofacial pain triggered by various stimuli), endothelin receptors might constitute new targets for treatment of this disorder.
 ...
PMID:Orofacial cold hyperalgesia due to infraorbital nerve constriction injury in rats: reversal by endothelin receptor antagonists but not non-steroidal anti-inflammatory drugs. 1693 96