Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0020440 (hypercapnia)
 7,939 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We investigated the effects of exogenous leukotriene D4, synthesis inhibitors, and a leukotriene receptor antagonist upon chloralose anesthetized, mechanically ventilated, neonatal piglets with constant left pulmonary blood flow and upon piglets with uncontrolled pulmonary blood flow. Leukotriene D4 (100-10,000 ng, intravenously) caused dose-dependent increases in peak tracheal pressure, pulmonary vascular resistance, and systemic arterial pressure. In a limited number of experiments, cardiovascular responses to exogenous leukotriene C4 were qualitatively similar but quantitatively less than those to leukotriene D4. Neither treatment with diethylcarbamazine or the lipoxygenase inhibitor nordihydroguaiaretic acid, nor with the leukotriene receptor antagonist, FPL55712, altered any baseline cardiovascular parameter measured, suggesting the absence of any influence of leukotrienes on resting hemodynamics. Hypoxia or hypoxia combined with mild hypercapnia caused pulmonary vasoconstriction. Neither treatment with diethylcarbamazine or the lipoxygenase inhibitor nordihydroguaiaretic acid, nor with the leukotriene receptor antagonist FPL55712, altered the pulmonary vasoconstrictor response to hypoxia or combined hypoxia/hypercapnia. We conclude that endogenous leukotrienes do not appear to have an influence on resting cardiovascular function, neither do they appear to be necessary for hypoxic pulmonary vasoconstriction in the neonatal piglet, although exogenous leukotrienes are capable of producing cardiovascular effects.
 ...
PMID:Cardiovascular effects of leukotrienes in neonatal piglets. Role in hypoxic pulmonary vasoconstriction? 649 33

The hypothesis that endothelium-dependent components contribute to the cerebromicrovascular dilation to hypoxia in the newborn pig was addressed. Piglets anesthetized with ketamine-acepromazine and maintained on alpha-chloralose were equipped with closed cranial windows. Injury to the endothelium of pial arterioles was produced by light activation of fluorescein dye. Light/dye injury reduced the pial arteriolar dilation to hypoxia (5 min, arterial PO2 approximately 30 mmHg) from 57 +/- 9 to 19 +/- 5%. Light/dye injury abolished the pial arteriolar dilation to hypercapnia but did not affect dilation to sodium nitroprusside. The pial arteriolar dilation to hypoxia was not affected by tetrodotoxin, N(omega)-nitro-L-arginine, glibenclamide, iberiotoxin, charybdotoxin, tetraethylammonium, or 8-phenyltheophylline. Hypoxia caused increases in the cerebral cortical production of adenosine 3',5'-cyclic monophosphate and guanosine 3',5'-cyclic monophosphate. Cerebral vasodilation to hypoxia was inhibited by 5,8,11,14-eicosatetraynoic acid but was not greatly affected by cyclooxygenase or lipoxygenase inhibitors. In contrast, the cytochrome P-450 epoxygenase inhibitor miconazol decreased cerebral vasodilation to hypoxia from 45 +/- 5 to 17 +/- 4%. Therefore, the vascular endothelium appears to participate in cerebral microvascular dilation to hypoxia in newborn pigs. The mechanism may include cytochrome P-450 epoxygenase metabolites of arachidonic acid.
 ...
PMID:Mechanisms of hypoxia-induced cerebrovascular dilation in the newborn pig. 908 8

PUFAs are precursors to bioactive oxylipin metabolites that increase in the brain following CO2-induced hypercapnia/ischemia. It is not known whether the brain-dissection process and its duration also alter these metabolites. We applied CO2 with or without head-focused microwave fixation for 2 min to evaluate the effects of CO2-induced asphyxiation, dissection, and dissection time on brain oxylipin concentrations. Compared with head-focused microwave fixation (control), CO2 followed by microwave fixation prior to dissection increased oxylipins derived from lipoxygenase (LOX), 15-hydroxyprostaglandin dehydrogenase (PGDH), cytochrome P450 (CYP), and soluble epoxide hydrolase (sEH) enzymatic pathways. This effect was enhanced when the duration of postmortem ischemia was prolonged by 6.4 min prior to microwave fixation. Brains dissected from rats subjected to CO2 without microwave fixation showed greater increases in LOX, PGDH, CYP and sEH metabolites compared with all other groups, as well as increased cyclooxygenase metabolites. In nonmicrowave-irradiated brains, sEH metabolites and one CYP metabolite correlated positively and negatively with dissection time, respectively. This study presents new evidence that the dissection process and its duration increase brain oxylipin concentrations, and that this is preventable by microwave fixation. When microwave fixation is not available, lipidomic studies should account for dissection time to reduce these artifacts.
 ...
PMID:Brain oxylipin concentrations following hypercapnia/ischemia: effects of brain dissection and dissection time. 3046 86