ABSTRACT
The mechanisms underlying cardiovascular diseases induced by chronic exposure to arsenic remain unclarified. The objectives of this study were to investigate whether increased vascular leakage is induced by inflammatory mustard oil in mice systemically exposed to various doses of arsenic and whether an increased vascular leakage response is still present in arsenic-fed mice after arsenic discontinuation for 2 or 6 months. ICR mice were fed water or various doses of sodium arsenite (10, 15, or 20 mg/kg/day; 5 days/week) for 8 weeks. In separate experiments, the mice were treated with sodium arsenite (20 mg/kg) for 2 or 8 weeks, followed by arsenic discontinuation for 2 or 6 months. Vascular permeability to inflammatory mustard oil was quantified using Evans blue (EB) techniques. Both arsenic-exposed and water-fed (control) mice displayed similar basal levels of EB leakage in the ears brushed with mineral oil, a vehicle of mustard oil. The levels of EB leakage induced by mustard oil in the arsenic groups fed with sodium arsenite (10 or 15 mg/kg) were similar to those of water-fed mice. However, increased levels of EB leakage in response to mustard oil stimulation were significantly higher in mice treated with sodium arsenite (20 mg/kg; high dose) than in arsenic-fed (10 or 15 mg/kg; low and middle doses) or control mice. After arsenic discontinuation for 2 or 6 months, mustard oil-induced vascular EB leakage in arsenic-fed (20 mg/kg) mice was similar to that in control mice. Dramatic increases in mustard oil-induced vascular leakage were only present in mice systemically exposed to the high arsenic dose, indicating the synergistic effects of the high arsenic dose and mustard oil.
Subject(s)
Arsenites/toxicity , Capillary Permeability/drug effects , Cardiovascular Diseases/physiopathology , Inflammation/physiopathology , Sodium Compounds/toxicity , Animals , Cardiovascular Diseases/chemically induced , Evans Blue , Humans , Inflammation/chemically induced , Mice , Mice, Inbred ICR , Mustard Plant/toxicity , Plant Oils/toxicityABSTRACT
Previous studies have shown that hyperthermia pretreatment results in an attenuation of increased vascular leakage in rats subjected to experimental anaphylactic shock. It is known that both nitric oxide synthase (NOS) and heme oxygenase-1 (HO-1) play a role in the maintenance of microvascular integrity. In the study, we investigated the effect of hyperthermia pretreatment on mRNA expression of endothelial NOS (eNOS), inducible NOS (iNOS), and HO-1 in heated or nonheated rats subjected to anaphylactic shock using a semi-quantitative RT-PCR. Protein contents of eNOS and HO-1 in tissue were also assayed. Plasma nitrite and nitrate before and after induction of anaphylactic shock were quantified using a NO analyzer. The heated, anaphylactic rats showed a significant increase of HO-1 mRNA expression in heart as compared to both non-heated, anaphylactic and control rats. HO-1 protein contents in both heart and lung tissues in the heated, anaphylactic rats were significantly higher than both non-heated, anaphylactic and control rats. Protein contents of eNOS in various tissues appeared to be the same among groups. No significant change of iNOS mRNA expression was detected among groups. Plasma nitrite and nitrate before and after anaphylactic treatment appeared to be the same among groups. These data suggest that reduction of anaphylactic hypotension by hyperthermia pretreatment in rats subjected to anaphylactic shock may be resulted from over-expression of HO-1 rather than NOS in various tissues.
Subject(s)
Anaphylaxis/physiopathology , Heme Oxygenase-1/biosynthesis , Hyperthermia, Induced , Nitric Oxide Synthase/biosynthesis , Animals , Gene Expression , HSP70 Heat-Shock Proteins/biosynthesis , Heme Oxygenase-1/genetics , Male , Nitrates/blood , Nitric Oxide Synthase Type II/genetics , Nitric Oxide Synthase Type III/genetics , Nitrites/blood , Polymerase Chain Reaction , RNA, Messenger/analysis , Rats , Rats, WistarABSTRACT
Previous studies indicate that intravenous infusion of CGS 26303, an endothelin-converting enzyme inhibitor, prevents and reverses cerebral vasospasm after experimental subarachnoid hemorrhage. Attenuation of the vasospastic response could result from enhanced production of nitric oxide via activation of endothelial nitric oxide synthase, neuronal nitric oxide synthase, or inducible nitric oxide synthase in brain tissue. Carbon monoxide has the same attenuation effect and is synthesized by inducible heme-oxygenase- 1 or constitutive heme-oxygenase-2. In this study, we investigated the effect of endothelin-converting enzyme inhibitor on mRNA expression of endothelial nitric oxide synthase, neuronal nitric oxide synthase, inducible nitric oxide synthase, heme-oxygenase- 1 and heme-oxygenase-2 in brain tissue of rats subjected to subarachnoid hemorrhage using semi-quantitative reverse transcription-polymerase chain reaction. The results showed that gene expression of inducible nitric oxide synthase or HSP70 was not detected in all groups of rats (n = 5/group). Expression of endothelial nitric oxide synthase, neuronal nitric oxide synthase or heme-oxygenase-2 mRNA in brain tissue in the groups of subarachnoid hemorrhage or subarachnoid hemorrhage treated with endothelin-converting enzyme inhibitor appeared to be the same as compared with control rats. The subarachnoid hemorrhage rats treated with endothelin-converting enzyme inhibitor showed a significant increase in the levels of heme-oxygenase-1 mRNA expression as compared with both subarachnoid hemorrhage and control rats. These data suggest that the reduction of cerebral vasospasm by CGS 26303 in rats subjected to experimental subarachnoid hemorrhage may result from both over-expression of heme-oxygenase-1 in brain tissue and suppression of endothelin biosynthesis in basilar arteries.