Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Effects of azelnidipine, a dihydropyridine derivative, on stunned myocardium were examined in anesthetized open-chest dogs. The left anterior descending (LAD) coronary artery was ligated for 20 min and then released for 60 min. Dimethyl sulfoxide (DMSO), the solvent of azelnidipine, or azelnidipine (0.03, 0.1 or 0.3 mg/kg) was injected i.v. 20 min before ligation. Segment shortening was determined by sonomicrometry. The levels of high-energy phosphate were measured in 60-min reperfused hearts. Azelnidipine at 0.1 and 0.3 mg/kg significantly decreased diastolic blood pressure and increased % segment shortening. The increase in % segment shortening due to azelnidipine appeared to be abolished by propranolol and atropine pretreatment. Ischemia significantly decreased % segment shortening in all groups. The % segment shortening that had been decreased by ischemia recovered during reperfusion, but did not reach its preischemic level in each group. In the 0.1 and 0.3 mg/kg of azelnidipine-treated dogs, a significant enhancement of % segment shortening recovery during reperfusion was observed, as compared with that in the DMSO-treated dogs. Azelnidipine did not affect the high-energy phosphate levels in 60-min reperfused hearts. In conclusion, azelnidipine improved the contractile dysfunction in stunned myocardium, without any preservation of high-energy phosphate.
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PMID:Effects of azelnidipine, a dihydropyridine calcium antagonist, on myocardial stunning in dogs. 962 15

In hypoxia, ATP depletion causes cellular Ca(2+) increase, mitochondrial injury, and apoptosis in renal tubular cells. However, the molecular basis of these observations is incompletely delineated. IRPTC, a rat renal proximal tubular cell line, was treated with antimycin A, and disturbances in cytoplasmic calcium ([Ca(2+)]c) and mitochondrial calcium ion concentration ([Ca(2+)]m), dissipation of mitochondrial membrane potential (DeltaPsi(m)), cytochrome c release, and resultant apoptosis were examined. Pharmacologic targeting of L-type Ca(2+) channels in vitro and in vivo was used to clarify the involvement of voltage-dependent Ca(2+) channels during this process. In vitro studies indicated that ATP depletion-induced apoptosis was preceded by increased [Ca(2+)]c and [Ca(2+)]m before activation of mitochondrial signaling. Antagonizing L-type Ca(2+) channels offset these findings, suggesting [Ca(2+)]c and [Ca(2+)]m involvement. Azelnidipine administration ameliorated cellular and mitochondrial Ca(2+) accumulation, mitochondrial permeability transition, cytochrome c release, caspase-9 activation, and resultant apoptosis (15.8 +/- 0.8% versus 8.9 +/- 0.7%; P < 0.01). Similar effects of azelnidipine were substantiated in an in vivo ischemia/reperfusion injury model. There were fewer terminal-deoxynucleotidyl transferase mediated dUTP nick-end labeling-positive cells in the azelnidipine-treated group (0.322 +/- 0.038/tubule) as compared with the vehicle-treated group (0.450 +/- 0.041; P < 0.05), although the antiapoptotic effect was smaller in vivo than in vitro, partly as a result of distinct levels of Bax expression. It is proposed that voltage-dependent Ca(2+) channels are involved in cellular and mitochondrial accumulation of Ca(2+) subsequent to ATP depletion and play an important role in regulating mitochondrial permeability transition, cytochrome c release, caspase activation, and apoptosis.
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PMID:Blockade of calcium influx through L-type calcium channels attenuates mitochondrial injury and apoptosis in hypoxic renal tubular cells. 1533 81

Azelnidipine has been reported to have antioxidant effects and attenuates tubulointerstitial ischemia. The aim of the present study was to determine whether azelnidipine exerts additional renoprotective effects to angiotensin II receptor blockers (ARBs) in hypertensive patients with diabetic nephropathy and microalbuminuria. 45 hypertensive patients with diabetes mellitus and microalbuminuria who were already being treated with ARBs were enrolled in this study. Azelnidipine was added to the drug treatment of 30 patients (8 mg/day, n = 15, or 16 mg/day, n = 15) whilst the remaining 15 control patients were not treated with azelnidipine. In all patients, urinary 8-hydroxydeoxyguanosine (8-OHdG) levels and urinary liver-type fatty acid-binding protein (L-FABP) levels were significantly correlated (r = 0.587, p = 0.0006). However, urinary albumin excretion (UAE) was not correlated with the levels of urinary 8-OHdG (r = 0.1975, p = 0.2956) or urinary L-FABP (r = 0.2057, p = 0.2759). Azelnidipine significantly reduced UAE, urinary 8-OHdG and urinary L-FABP after 6 (p < 0.05) and 12 months (p < 0.05). Although blood pressure was comparable between the azelnidipine doses of 8 and 16 mg/day, the UAE (p < 0.05 after 12 months), urinary 8-OHdG (p < 0.05 after 6 and 12 months) and urinary L-FABP (p < 0.05 after 6 and 12 months) levels were more significantly reduced in patients receiving the higher dose of 16 mg/day. These data may suggest that the addition of azelnidipine treatment to therapy with ARBs has dose-dependent antioxidant and renoprotective effects beyond blood pressure-lowering effects in hypertensive diabetic nephropathy patients.
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PMID:Additional renoprotective effects of azelnidipine combined with angiotensin receptor blockers in patients with diabetic nephropathy. 1900 May 38

Effects of azelnidipine were examined and compared with those of amlodipine on stunned myocardium in dogs. The left anterior descending (LAD) coronary artery was ligated for 20 min and subsequently released for 60 min. A vehicle, azelnidipine (0.3 mg/kg), or amlodipine (0.3 or 1 mg/kg) was injected intravenously 20 min before LAD ligation. The heart rate increased after a depressor response in the presence of amlodipine, while it decreased despite a decrease in arterial pressures in the presence of azelnidipine. After reperfusion, the coronary flow (CF) significantly increased in the presence of azelnidipine, but did not change with amlodipine after reperfusion. A positive inotropic effect was observed after treatment with both calcium antagonists. Ischemia significantly decreased the percentage of segment shortening (%SS) in all groups. Treatment with both calcium antagonists significantly increased %SS after reperfusion, although high-energy phosphate levels did not improve in the presence of calcium antagonists 60 min after reperfusion. Mortality with azelnidipine was significantly lower than that with 0.3 mg/kg amlodipine immediately after reperfusion. In conclusion, improvement in myocardial stunning after pretreatment with azelnidipine is associated with an increase in CF after reperfusion. The negative chronotropic action may have contributed to decreased mortality due to reperfusion arrhythmias. Azelnidipine is more beneficial than amlodipine and may provide an additional advantage to patients with angina and hypertension.
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PMID:Comparative effects of azelnidipine and amlodipine on myocardial function and mortality after ischemia/reperfusion in dogs. 2159 38