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)

To examine the effects of nipradilol on ischemic myocardium, experiments were performed on regional myocardial blood flow (MBF) and energy metabolism in anesthetized, open-chest dogs. Nipradilol at a dose of 0.3 mg/kg was i.v.-administered 10 min after coronary ligation. MBFs at various sites, including ischemic and non-ischemic areas, were determined by the hydrogen gas clearance method. The levels of ATP and creatine phosphate (CP) at the site of MBF determination were measured 60 min after ligation, and mitochondrial function (RCI, QO2) in the ischemic and non-ischemic areas was determined. Following nipradilol administration, aortic pressure and heart rate were significantly lowered. In ischemic areas with MBF below 40 ml/min/100 g, nipradilol had no influence on MBF. However, the tissue level of ATP in nipradilol treated hearts was significantly higher as compared with untreated hearts. In the area of mild ischemia with MBF of 40-60 ml/min/100 g, nipradilol preserved the tissue ATP and CP levels in spite of a decrease in MBF. Moreover, an inhibition of the decrease in mitochondrial respiratory function was observed in ischemic areas with MBF below 20 ml/min/100 g. Thus, nipradilol administered following ischemia preserved ATP content and mitochondrial function in the ischemic myocardium with reduction of heart rate and aortic pressure. This suggests that nipradilol exerts a cardioprotective effect in acute ischemia. It seems that the cardioprotective effect is due to a decrease in myocardial oxygen demand and preservation of mitochondrial function.
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PMID:Beneficial effect of nipradilol (K-351) on acute myocardial ischemia. Study of the relationship between regional myocardial blood flow and energy metabolism. 196 87

We examined the effect of nicorandil and nipradilol on the ischemic myocardium in the isolated perfused rat heart. The heart was perfused by the working heart technique with an afterload pressure of 60 mm Hg and with a left atrial filling pressure of 9 mm Hg. Ischemia was induced for 20 min by lowering the afterload pressure. The afterload pressure was raised to 60 mm Hg again during reperfusion. Ischemia decreased the pressure-rate product, coronary flow, adenosine triphosphate level and creatine phosphate level, and increased the lactate level. Reperfusion could not restore the pressure-rate product nor the adenosine triphosphate level completely. Nicorandil (5 x 10(-5) and 1.5 x 10(-4) M) or nipradilol (10(-5), 5 x 10(-5) and 1.5 x 10(-4) M) was introduced 5 min before ischemia. Nipradilol preserved the levels of adenosine triphosphate and creatine phosphate after 20 min of ischemia and increased the extent of recovery of the pressure-rate product during reperfusion, whereas nicorandil did not. Nipradilol, but not nicorandil, can protect the myocardium against ischemic damage.
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PMID:Effects of nicorandil and nipradilol on ischemic myocardium in perfused rat heart. 252 96

In dogs anesthetized with pentobarbital, the anterior descending coronary artery (LAD) was partially occluded to reduce LAD flow to about half of the original flow (partial occlusion). Myocardial pH (MpH) was measured by the use of a micro glass pH electrode. MpH decreased from 7.5-7.63 to 6.82-6.86 30 min after partial occlusion of the LAD. Nipradilol (0.3 mg/kg) was injected intravenously 30 min after partial occlusion, which continued for a further 60 min after nipradilol injection. Nipradilol decreased blood pressure and heart rate, and significantly increased myocardial pH which had been decreased by partial occlusion, within 60 min after injection. Nipradilol-induced restoration of the myocardial [H+] (calculated from the pH data), that had been increased by partial occlusion, was 48.5%. Bradycardia induced by nipradilol was not a determinant factor in the pH effect of nipradilol, because even in the paced heart, nipradilol restored the myocardial [H+] that had been increased by partial occlusion. These results indicate that nipradilol attenuates ischemia-induced myocardial acidosis, suggesting the favorable effect of nipradilol on ischemic myocardium. The favorable effect of nipradilol may be due to the beta-adrenoceptor antagonistic effect rather than the vasodilating effect.
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PMID:Nipradilol, a beta-adrenoceptor antagonist having a vasodilatory action, attenuates myocardial acidosis induced by coronary artery occlusion in dogs. 256 18

The proliferative cell nuclear antigen (PCNA) is an auxiliary protein of DNA polymerase delta and appears to be required for both DNA synthesis and repair. Previously, we showed that prolonged NO synthase (NOS) inhibition produced severe nephrosclerosis with an increase of glomerular cell DNA fragmentation (apoptosis), glomerular ischemia and hypertension in spontaneously hypertensive rats (SHR). The objective of the present study was to investigate the effects of the vasodilating, nonselective, NO-releasing beta-adrenoceptor blocker nipradilol on DNA fragmentation and synthesis/repair of glomerular cells in this prolonged NOS blockaded SHR. Twenty-week-old SHR were administered an NOS inhibitor, N(G)-nitro-L-arginine methyl ester (L-NAME, 80 mg/l in drinking water) or co-treated with the same dose of L-NAME and nipradilol (20 mg/kg/day) for 3 weeks. After this treatment, expression of apoptosis was histologically examined using caspase-3, an apoptosis inducer, in addition PCNA (DNA synthesis/repair), and examination of glomerular morphometric changes, including cell number and tuft area. Nipradilol reduced blood pressure and preserved creatinine clearance reduction in L-NAME/SHR. These effects were associated with normalization of the glomerular cell apoptosis index and caspase-3 score, an increase in PCNA index, and increases in glomerular cell numbers and glomerular tuft area, resulting in a decreased glomerular injury score. Thus, in SHR administered an NOS inhibitor, nipradilol improved nephrosclerosis in association with a decrease in apoptosis and an increase in DNA synthesis/repair of glomerular cells. These findings may provide important insights into DNA repair/repair and apoptosis in nephrosclerosis.
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PMID:Nipradilol prevents L-NAME-exacerbated nephrosclerosis with decreasing of caspase-3 expression in SHR. 1213 23