Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0012739 (disseminated intravascular coagulation)
 8,673 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. The calcium channel blocker, nicardipine, produced a dose-dependent reduction in the mortality caused by endotoxin in rats. 2. The drug also reduced most of the hematological and gross pathological manifestations of disseminated intravascular coagulation (DIC) caused by endotoxin. 3. The endotoxin-induced monocytopenia but not the granulocytopenia, lymphocytopenia or thrombocytopenia was inhibited by the drug. 4. The results suggest that the protective action of nicardipine is causally related to prevention of the endotoxin-induced DIC and that an effect of the drug on monocytes may be of importance.
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PMID:Effects of nicardipine in rats subjected to endotoxic shock. 159 29

Treatment of endotoxemia is difficult because of the numerous mediators involved in the body's response to endotoxin. There are three possible approaches in treating endotoxemia. The interaction of endotoxin with target cells can be blocked by inducing tolerance, decreasing plasma endotoxin concentrations, or interfering with endotoxin binding. Once endotoxin has interacted with target cells, endogenous mediators can be blocked with a huge variety of drugs. The effects of corticosteroids, cyclooxygenase blockers, leukotriene blockers, platelet activating factor blockers, tumor necrosis factor blockers, oxygen radical scavengers, opiate antagonists, antihistamines, calcium channel blockers are detailed. Supportive care of the endotoxemic patient continues to be a critical aspect of treatment. Controversies regarding solutions to use for volume support, vasoactive and cardiostimulant drugs, metabolic support, and treatment of disseminated intravascular coagulation are reviewed.
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PMID:Endotoxic shock. Part II: A review of treatment. 207 55

The endothelium-derived hyperpolarizing factor (EDHF) serves as a back-up mechanism that compensates for reduced nitric oxide (NO)/prostanoids bioavailability. Here we investigated whether (i) under conditions of vascular endothelium dysfunction, the immunosuppressant drug cyclosporine (CSA) upregulates EDHF-dependent renal vasodilations through altering CYP4A/CYP2C signaling, and (ii) calcium channel blockers modulate the CSA/EDHF/CYP interaction. Rats were treated with CSA, verapamil, nifedipine, or their combinations for 7days. Blood pressure (BP) was measured by tail-cuff plethysmography. Kidneys were then isolated, perfused with physiological solution containing L-NAME (NOS inhibitor) and diclofenac (cyclooxygenase inhibitor, DIC), and preconstricted with phenylephrine. CSA (25mgkg-1day-1 for 7days) increased BP and augmented carbachol renal vasodilations. The co-treatment with verapamil (2mgkg-1day-1) or nifedipine (3mgkg-1day-1) abolished CSA hypertension and conversely affected carbachol vasodilations (increases vs. decreases). Infusion of MSPPOH (epoxyeicosatrienoic acids, EETs, inhibitor) reduced carbachol vasodilations in kidneys of all rat groups, suggesting the importance of EETs in these responses. By contrast, 20-Hydroxyeicosatetraenoic Acid (20-HETE) inhibition by HET0016 increased carbachol vasodilations in control rats, an effect that disappeared by CSA treatment, and reappeared in rats treated with CSA/verapamil or CSA/nifedipine. Renal protein expression of CYP2C and CYP4A as well as their vasoactive products (EETs/20-HETE) were increased in CSA-treated rats. Whereas the CYP2C/EETs effects of CSA were abolished by verapamil and intensified by nifedipine, the CYP4A/20-HETE effects were reduced by either CCB. Overall, nifedipine and verapamil blunts CSA hypertension but variably affected concomitantly enhanced EDHF-dependent renal vasodilations and alterations in CYP2C/CYP4A signaling.
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PMID:CYP4A/CYP2C modulation of the interaction of calcium channel blockers with cyclosporine on EDHF-mediated renal vasodilations in rats. 2889 49