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PubMed1992

Inhibitory action of dilazep on histamine-stimulated cytosolic Ca2+ increase in cultured human endothelial cells.

Using a fluorescent Ca(2+)-sensitive dye, fura-2, and photometric fluorescence microscopy, we measured changes in cytosolic Ca2+ concentration ([Ca2+]i) in cultured human endothelial cells and studied the effect of dilazep on [Ca2+]i elevation induced by histamine. Histamine (1 microM) caused a rapid transient peak in the average [Ca2+]i of a group of cells (approximately 10(2) cells), followed by a decrease to a sustained elevation. Dilazep as well as diltiazem (1.0 to 100 microM) concentration-dependently inhibited the latter sustained elevation, which was eliminated by removal of extracellular Ca2+, while the initial transient response was not changed by dilazep at concentrations up to 100 microM. The IC50 values of dilazep and diltiazem were 16 and 58 microM, respectively. The patterns of the [Ca2+]i elevation responses to histamine were variable among individual cells. Some single cells showed a transient peak and a sustained elevation as observed in a group of cells. Some single cells caused a repetitive spikelike elevation of [Ca2+]i. Dilazep lowered the sustained elevation to the resting level and in some single cells, changed the sustained elevation to the spikelike elevation. The frequency of the spikelike [Ca2+]i elevation was also decreased by dilazep. Decrease in extracellular [Ca2+] showed the same pattern of inhibitory actions as dilazep did. These results indicate that dilazep inhibits the extracellular Ca2+ influx in endothelial cells.

Calcium↗
PubMed1999

Cross over placebo control trial of dilazep in beta-thalassemia/hemoglobin E patients.

An attempt was made to find better symptomatic treatment for beta-thalassemia/hemoglobin E (beta-thal/Hb E) patients in order to reduce their blood demand. Oral administration of dilazep was prescribed for these patients and a clinical trial was conducted over a 2-year period as a cross over placebo control study. Seventeen beta-thal/Hb E patients were enrolled in the study. All of them received dilazep and placebo for 10 months at different periods of time and were taken care of by the same doctor throughout the study. The blood demand of the same patients during the period of receiving dilazep with the period of receiving placebo, was 1.5 +/- 1.8 U/10 months versus 2.2 +/- 2.6 U/10 months, respectively. Thus dilazep showed a benefit in decreasing the blood demand by about 50% although the results did not reach statistical significance (p = 0.1). There was a statistical difference in hemoglobin concentration of the patients receiving dilazep compared with placebo (p = 0.038). While receiving dilazep the mean +/- SD hemoglobin level was 5.82 +/- 0.8 g/dl, significantly higher than while receiving placebo (5.66 +/- 0.9 g/dl) (p = 0.038). The liver, and renal function tests, and cardiac enzyme levels of the patients showed no significant changes throughout the study. However, one case had a problem with bleeding following tooth extraction whilst receiving dilazep and needed 1 unit of blood transfusion. In conclusion, administration of dilazep to patients with beta-thal/Hb E increased the patients' hemoglobin and reduced their blood demand with few side effects.

Adolescent↗
PubMedDate not supplied

Dilazep inhibits binding of batrachotoxin to sodium channels in canine sarcolemmal vesicles.

We studied the effect of dilazep on the binding of [3H]- batrachotoxinin A 20 alpha-benzoate ([3H]BTXB), which binds to and stabilizes the activated state of the Na+ channel, and compared it with that of lidocaine in canine cardiac sarcolemmal vesicles. Dilazep inhibited the specific [3H]BTXB binding in a dose-dependent manner with an IC50 value of 0.37 microM, while lidocaine inhibited it with an IC50 value of 92 microM. Scatchard analysis of [3H]BTXB binding demonstrated that both dilazep and lidocaine reduced the amax without a marked effect on the K(D). The inhibition of [3H]BTXB induced by dilazep was reversible. Both dilazep (4 microM) and lidocaine (100 microM) increased the dissociation rate constant of [3H]BTXB only in concentrations which are about a 10-fold greater than their IC50, indicating the low affinity of both drugs for the [3H]BTXB-bound Na+ channel. However, dilazep (0.5 microM) and lidocaine (100 microM) decreased significantly the association rate constant of the [3H]BTXB binding at concentrations near their IC50, indicating that the affinity of both drugs for the [3H]BTXB-unbound Na+ channel is relatively high. These results suggest that, in canine cardiac membrane vesicles, the effect of dilazep in inhibiting the binding of [3H]BTXB and stabilizing the Na+ channel is similar to that of lidocaine, but the potency of dilazep is greater than that of lidocaine.

Aconitine↗
PubMed1997

Protective effects of dilazep and its derivative K-7259 on the haemolysis induced by amphiphiles in rat erythrocytes.

The effects of dilazep and K-7259, a dilazep derivative, on the haemolysis (as evidenced by release of haemoglobin) induced by palmitoyl-L-carnitine (PAL-CAR) or palmitoyl 1-alpha-lysophosphatidylcholine (PAL-LPC) have been determined in rat erythrocytes. At concentrations above the critical micelle concentration both PAL-CAR and PAL-LPC induced haemolysis; the concentrations of PAL-CAR and PAL-LPC producing 50% haemolysis were approximately 13 and 14 microM, respectively. The 50% haemolysis induced by PAL-CAR or PAL-LPC was attenuated by dilazep (1, 10 or 100 microM) but not at the highest concentration used (1 mM). K-7259 attenuated the 50% haemolysis induced by PAL-CAR or PAL-LPC at concentrations ranging from 1 microM to 1 mM. Similarly, dilazep (1 to 100 microM) and K-7259 (1 microM to 1 mM) significantly or insignificantly attenuated the 25% and 75% haemolysis induced by PAL-CAR or PAL-LPC. Neither dilazep nor K-7259 affected micelle formation by PAL-CAR or PAL-LPC, nor, at concentrations of 1 and 10 microM, did they attenuate the haemolysis induced by osmotic imbalance (hypotonic haemolysis). These results suggest that both dilazep and K-7259 protect the erythrocyte membrane from the damage induced by PAL-CAR or PAL-LPC. The protective effects of dilazep and K-7259 are mediated by some mechanism other than prevention of micelle formation or protection of the erythrocyte membrane against osmotic imbalance.

Animals↗
PubMed1993

The effect of dilazep on urinary protein excretion in spontaneous diabetic Chinese hamster.

The effect of dilazep, an adenosine potentiator and platelet aggregation inhibitor, on experimental diabetic nephropathy was investigated in spontaneous diabetic Chinese hamster. Prediabetic animals, 8 weeks of age, were divided into two groups. In one group, 5 mg/kg dilazep was injected i.p. once a day. In the other group, saline of the same amount was injected. Age- and sex-matched animals from a nondiabetic subline were used as controls. No difference was observed in body weight, mean blood pressure, fasting plasma glucose and glycated hemoglobin level between diabetic animals with and without dilazep administration throughout the entire period of experiment. Urinary protein excretions in untreated diabetic animals increased significantly compared to those of nondiabetic controls at 8 weeks (17.5 +/- 3.5 vs 2.0 +/- 0.1 mg/day), and at 24 weeks (25.3 +/- 5.1 vs 2.7 +/- 0.1 mg/day) of experiment. In diabetic animals with dilazep treatment, urinary protein excretions (4.1 +/- 0.7 at 8 weeks and 13.1 +/- 2.9 mg/day at 24 weeks of experiment) were significantly suppressed compared to those in untreated diabetic animals. Significant thickening of glomerular basement membrane (GBM) was observed in diabetic animals both with and without dilazep administration at 24 weeks of experiment compared to that in nondiabetic controls. The number of anionic sites in GBM, stained by polyethyleneimine, was reduced in untreated diabetic animals, but was not different in dilazep treated animals compared to that in nondiabetic controls. It was concluded that dilazep administration suppressed urinary protein excretion in diabetic Chinese hamster possibly through the preservation of charge barrier of the glomerulus.

Animals↗
PubMed1981

Effect of dilazep on myocardial contractility following acute ischemia and reperfusion in isolated blood-perfused canine left ventricular muscle.

Myocardial protection by dilazep HCl, an antianginal drug and a potent calcium antagonist, against myocardial damage following acute ischemia and reperfusion was studied with respect to myocardial contractility in isolated blood-perfused canine left ventricular muscle. Myocardial function was expressed by percent recovery rate of maximal net developed tension. 1) The coronary infusion of dilazep revealed significant myocardial protection during normothermic ischemic arrest of 45 min and reperfusion. 2) The intravenous administration of dilazep to the support dog and Young's infusion also showed significant myocardial protection during normothermic ischemic arrest of 45 min and reperfusion. Dilazep showed no persistent depression of myocardial contractility due to its calcium antagonistic effect during reperfusion. 3) The combination of intravenous administration of dilazep to the support dog, Young's infusion, and hypothermia showed significant myocardial protection during prolonged ischemia and reperfusion even in hypertrophied ventricle. These results demonstrate that dilazep provides effective myocardial protection during ischemic arrest and reperfusion by preventing abnormal calcium accumulation in myocardial cells during reperfusion. No persistent depression of myocardial contractility during reperfusion may support dilazep's clinical application as a myocardial protective agent in open-heart surgery.

Animals↗
PubMed1989

Effects of dilazep on cytoplasmic calcium ion concentrations and arachidonic acid metabolism in activated human platelets.

The effects of dilazep (tetrahydro-1H-1,4-diazepine-1,4(5H)-dipropanol bis(3,4,5-trimethoxybenzoate)-di-hydrochloride monohydrate, Comelian), a coronary and cerebral vasodilator and an antiplatelet drug, on the cytoplasmic Ca2+ concentration ([Ca2+]i) and arachidonic acid (AA) metabolism in activated human platelets were investigated. [Ca2+]i (free calcium ion concentration) of aequorin-loaded platelets was estimated by using the platelet ionized calcium aggregometer. AA metabolism was studied by the determination of AA metabolites, hydroxyheptadecatrienoic acid and 12-hydroxyeicosatetraenoic acid, using reversed-phase high performance liquid chromatography. When platelets were preincubated with dilazep (0-0.5 mmol/l), the drug inhibited both platelet aggregation and [Ca2+]i elevation induced by thrombin, AA and collagen in a concentration dependent manner, while only aggregation was inhibited after stimulation with the Ca ionophore A23187 (calcimycin). Both influx and release of Ca2+ into platelet cytoplasm induced by thrombin or AA were inhibited by dilazep, while neither of them was affected when induced by A23187. Oral ingestion of dilazep as a 100-mg capsule significantly depressed the [Ca2+]i elevation induced by thrombin, AA and collagen after 3 h. Dilazep inhibited endogenous AA metabolism by platelets induced by thrombin, although it enhanced exogenous one. Thus, dilazep inhibited platelet aggregation induced by any agonists including A23187, while [Ca2+]i elevation was inhibited by the drug only when the receptor-mediated agonist was used. Furthermore, it is suggested that dilazep inhibited AA liberation from platelet membrane phospholipids, leading to reduced production of all endogenous AA metabolites after platelet activation although metabolites of exogenous AA could be increased.

Adult↗
PubMed1987

The effect of dilazep on puromycin-induced rat renal mitochondrial dysfunction.

The effect of tetrahydro-1 H-1,4 (5H)-dipropanol bis(3,4,5-trimethoxybenzoate)hydrochloride monohydrate (dilazep, Comelian) on puromycin-induced rat renal damage was investigated. In vivo study: Rats were divided into 3 groups, the control group; untreated, the puromycin group; puromycin (150 mg/kg) was injected intraperitoneally once, the dilazep + puromycin group; puromycin (150 mg/kg) was injected 1 h after intraperitoneal dilazep injection (2 mg/kg), and dilazep (2 mg/kg) was injected every 12 h until the end of the experiment. In each group, 84 h after puromycin injection, kidneys were isolated and renal mitochondria were prepared. The endogenous phospholipase activity in kidney homogenate was determined by high performance liquid chromatography. The activities of three segments (NADH-cytochrome c reductase, succinate-cytochrome c reductase and cytochrome c oxidase) of the electron-transport chain in mitochondria were measured enzymatically. In the puromycin group, phospholipase activity was increased and activities of all of three segments of the electron-transport chain were decreased. In the dilazep + puromycin group, premedication with dilazep prevented activation of phospholipase and maintained mitochondrial electron-transport activity. In vitro study: Mitochondria prepared from intact rat kidney were incubated with phospholipase C. Activities of the mitochondrial electron-transport chain were deteriorated by phospholipase C. These results indicated that activation of endogenous phospholipase, which digests membrane phospholipids, essential components in maintaining mitochondrial electron-transport activity, is responsible for the puromycin-induced renal damage. Premedication with dilazep prevented the damage by inhibition of the activation of phospholipase.

Animals↗
PubMed1996

Protective effects of dilazep and its novel derivative, K-7259, on mechanical and metabolic derangements induced by hydrogen peroxide in the isolated perfused rat heart.

The effect of dilazep, a potentiator of the adenosine-mediated effects, on the hydrogen peroxide (H2O2)-induced mechanical and metabolic derangements was studied in the isolated rat heart, and compared with that of K-7259, a dilazep derivative having less potentiating action on the adenosine-mediated effects. The heart was perfused aerobically by Langendorff's technique at a constant flow and driven electrically. H2O2 (600 microM) decreased the left ventricular developed pressure and increased the left ventricular end diastolic pressure in the heart (i.e, mechanical dysfunction), decreased the tissue ATP level and increased the tissue AMP level (i.e., metabolic change) and increased the tissue level of malondialdehyde (i.e., lipid peroxidation). These mechanical and metabolic alterations induced by H2O2 were attenuated by dilazep (1 microM), and the effect of dilazep was not modified by 8-(p-sulfophenyl)-theophylline (20 microM), a nonselective adenosine receptor antagonist. K-7259 (1 microM) also attenuated the H2O2-induced mechanical and metabolic derangements. Nevertheless, neither dilazep nor K-7259 modified the tissue malondialdehyde level, which was increased by H2O2, and the mechanical function and energy metabolism of the normal (H2O2-untreated) heart. These results suggest that both dilazep and K-7259 attenuate mechanical and metabolic derangements induced by H2O2. The protective action of dilazep and K-7259 on the H2O2-induced derangements is not due to potentiation of adenosine-mediated effects, reduction of lipid peroxidation or preservation of energy.

Animals↗
PubMed1992

Effect of dilazep dihydrochloride against ischemia and reperfusion-induced disruption of blood-brain barrier in rats: a quantitative study.

The effect of dilazep dihydrochloride (dilazep) against ischemia and reperfusion-induced disruption of blood-brain barrier (BBB) was quantitatively investigated in Slc:Wistar strain rats using Evans blue dye as a BBB destruction indicator. The forebrain of sham-operated animal had a small amount of the dye. A treatment of 3.5-h ischemia plus 2-h reflow extravasated the dye into the brain and markedly increased the dye content as compared with that of sham group (P less than 0.01 vs. sham group). Continuous infusion (i.v.) of dilazep during cerebral ischemia dose-dependently reduced the increase of the dye content, and a significant reduction was found at 3 mg/kg/h (P less than 0.05 vs. control group). Evans blue dye extravasation after ischemia was also greatly reduced in saline-perfused brains by the treatment with dilazep. Dilazep has been reported to inhibit edema formation in cerebral ischemia model of spontaneously hypertensive rats. These results suggest that dilazep prevents the ischemic damage of BBB, which may contribute to reduction of the brain edema.

Animals↗
PubMed1984

Effects of dilazep on coronary and systemic hemodynamics in humans.

The cardiovascular effects of dilazep, a new antianginal drug, were investigated in 18 patients, who underwent cardiac catheterization and coronary angiography for the evaluation of chest pain. Dilazep, 0.2 mg/kg, was injected intravenously over 1 to 2 minutes. The changes induced by dilazep in coronary tone were assessed by quantitative angiography in four patients, changes in systemic and coronary hemodynamics and blood gases in eight patients, and changes in systemic and pulmonary hemodynamics and blood gases in six. In 6 of the 18 patients the effects on hemoglobin-O2 oxygen binding were also investigated. Following dilazep administration, we observed a marked reduction of coronary resistance (six patients) (0.5 vs 1.0 mm Hg X min X ml-1, p less than 0.01) and of aortic-coronary sinus oxygen difference (seven patients) (4.6 vs 12.3 vol%, p less than 0.01), and a 23% increase in coronary diameter (four patients) (p less than 0.001). Total systemic resistance was also reduced by dilazep (six patients). Conversely, only minimal or insignificant changes were observed in heart rate (14 patients), aortic pressure (14 patients), total pulmonary resistance (six patients), myocardial oxygen consumption (six patients), double product (14 patients), blood gases (seven patients), and hemoglobin-oxygen affinity (six patients). We conclude that dilazep exerts a powerful dilating action on coronary vasculature without appreciable increase of myocardial oxygen consumption and cardiac work simultaneously with a reduction of peripheral resistance.

Adult↗
PubMed1988

Species differences in sensitivity of nucleoside transport in erythrocytes and cultured cells to inhibition by nitrobenzylthioinosine, dipyridamole, dilazep and lidoflazine.

Differences in sensitivity of uridine transport in erythrocytes and cultured cells to inhibition by dipyridamole, dilazep and lidoflazine were largely species-specific; uridine transport in human cells, and probably in pig and rabbit cells, was 2-3- and 10-times more sensitive to inhibition by dipyridamole (IC50 approx. 50 nM) and about 10- and 20-times more sensitive to dilazep inhibition (IC50 approx. 5 nM) than transport in mouse and rat cells, respectively. Uridine transport in human erythrocytes and HeLa cells was strongly inhibited by lidoflazine (IC50 10-140 nM), whereas that in both mouse and rat cells was highly resistant (IC50 greater than 10 microM). Superimposed on species-specific differences were some cell type specific differences in sensitivity of nucleoside transport to these inhibitors. Uridine transport in Walker 256 rat carcinoma cells was more resistant to dipyridamole and dilazep than that of other rat cells. Transport in human Hep-2 cells was more resistant to lidoflazine (IC50 2000 nM) than that of human erythrocytes and HeLa cells, whereas it showed similar sensitivity to dilazep and dipyridamole. Uridine transport in Chinese hamster cells was also more resistant to dilazep than that of baby hamster kidney cells. In addition HeLa cells and clones thereof expressed uridine transporters (about 50% each) with difference of about 1000-fold in sensitivity to inhibition by dilazep (IC50 approx. 5 nM and 5 microM, respectively).

Animals↗
PubMed1983

Dilazep-induced reduction of ischemic necrosis in rats with coronary artery occlusion.

To assess whether dilazep reduces myocardial necrosis we assigned 72 rats that survived coronary artery occlusion to 3 groups. The first control group (n = 26) received coronary occlusion and was untreated. The second group (n = 21) received coronary occlusion and was treated with dilazep (150 micrograms/kg s.c.) every 8 hours for 48 hours. The third group (n = 25) was sham-operated. Forty-eight hours later the creatine-kinase activity of the left ventricle was measured. The calculated left ventricular fraction that survived the occlusion was larger in dilazep-treated rats (44.5 +/- 4.1% of left ventricle) than in controls (31.2 +/- 3.2%; P less than 0.05). Twenty-six more rats also underwent coronary occlusion; 12 were controls and the remaining 14 were treated with dilazep at the same time and dose as before and killed 21 days after occlusion. Infarct size was evaluated on histological sections of the hearts by planimetry. The amount of left ventricle preserved from necrosis was larger in dilazep-treated rats, 82.1 +/- 0.9%, compared to controls 69.5 +/- 1.4% (P less than 0.05). Dilazep seems effective in preserving myocardial tissue from ischemic necrosis, and its beneficial effects are long-lasting, producing permanent reduction of infarct size.

Animals↗
PubMed1989

Effects of dilazep in evolving myocardial infarction in dogs: a biochemical study.

Mongrel dogs of either sex with ligation of their left anterior descending coronary artery were employed for the present study to investigate the biochemical basis of the cardioprotective action of dilazep. Dilazep (0.2 mg/kg intravenous) was administered 20 minutes after coronary arterial occlusion. Ligation of the artery for 40 minutes increased the tissue lactate concentration and decreased the adenosine triphosphate molecules within the occluded bed. Dilazep decreased the lactate concentration and improved the adenosine triphosphate content of this bed significantly. Dilazep also lowered the tissue cyclic adenosine monophosphate concentration and free fatty acid extraction of the ischemic myocardium as studied 40 minutes after coronary arterial ligation. It can be inferred that less free fatty acid extraction and calcium antagonistic action of dilazep helps in restoring mitochondrial function. Furthermore, decreased tissue lactate concentration resulted after better perfusion of the occluded bed and helped in greater generation of adenosine triphosphate molecules. These favorable biochemical and metabolic changes contribute to the cardioprotective action of dilazep.

Adenosine Triphosphate↗
PubMed2003

Dilazep and fenofibric acid inhibit MCP-1 mRNA expression in glycoxidized LDL-stimulated human endothelial cells.

We previously reported that glycoxidized low-density lipoprotein (glycoxidized LDL) enhanced monocyte chemoattractant protein-1 (MCP-1) mRNA expression through activation of nuclear factor-kappaB (NF-kappaB). Here we investigated the effects of dilazep, an anti-platelet agent, and fenofibric acid, an active metabolite of fenofibrate, on glycoxidized low-density lipoprotein-(LDL)-enhanced MCP-1 mRNA expression. Both 10 microg/ml dilazep and 100 microM fenofibric acid abrogated MCP-1 mRNA expression. ZM241385, an A2a adenosine receptor antagonist, partially inhibited the suppressive effect of dilazep. NF-kappaB activity was also suppressed by 1 microg/ml dilazep and 10 microM fenofibric acid. The antioxidative activity of these drugs on glycation to native LDL or oxidation to glycated LDL was measured using lipid peroxidation and lyso-phosphatidylcholine contents in LDL. Dilazep but not fenofibric acid exhibited antioxidative activity. Although the mechanisms of anti-atherogenic effects of the two drugs on glycoxidized LDL are different, both dilazep and fenofibric acid could potentially prevent atherosclerosis in diabetes mellitus.

Cells, Cultured↗
PubMed2001

Mutation of residue 33 of human equilibrative nucleoside transporters 1 and 2 alters sensitivity to inhibition of transport by dilazep and dipyridamole.

Human equilibrative nucleoside transporters (hENT) 1 and 2 differ in that hENT1 is inhibited by nanomolar concentrations of dipyridamole and dilazep, whereas hENT2 is 2 and 3 orders of magnitude less sensitive, respectively. When a yeast expression plasmid containing the hENT1 cDNA was randomly mutated and screened by phenotypic complementation in Saccharomyces cerevisiae to identify mutants with reduced sensitivity to dilazep, clones with a point mutation that converted Met33 to Ile (hENT1-M33I) were obtained. Characterization of the mutant protein in S. cerevisiae and Xenopus laevis oocytes revealed that the mutant had less than one-tenth the sensitivity to dilazep and dipyridamole than wild type hENT1, with no change in nitrobenzylmercaptopurine ribonucleoside (NBMPR) sensitivity or apparent uridine affinity. To determine whether the reciprocal mutation in hENT2 (Ile33 to Met) also altered sensitivity to dilazep and dipyridamole, hENT2-I33M was created by site-directed mutagenesis. Although the resulting mutant (hENT2-I33M) displayed >10-fold higher dilazep and dipyridamole sensitivity and >8-fold higher uridine affinity compared with wild type hENT2, it retained insensitivity to NBMPR. These data established that mutation of residue 33 (Met versus Ile) of hENT1 and hENT2 altered the dilazep and dipyridamole sensitivities in both proteins, suggesting that a common region of inhibitor interaction has been identified.

Amino Acid Sequence↗
PubMed1987

Effects of verapamil, nifedipine, and dilazep on left ventricular relaxation in the conscious dog.

The cardiac systolic and diastolic effects of the two major calcium blockers, verapamil and nifedipine, were studied and compared with those produced by dilazep, a relatively new vasodilator with calcium blocking properties, in conscious instrumented dogs to avoid the complications of anaesthesia and recent surgery. Mean arterial pressure was reduced by nifedipine and dilazep but not by verapamil, whereas peak left ventricular pressure was reduced only by dilazep and verapamil. Consistent tachycardia occurred, the rate being highest with nifedipine and lowest with dilazep. Left ventricular dP/dt was unaffected by dilazep, reduced by verapamil, and increased by nifedipine; this increase was no longer observed after beta adrenergic blockade. Ventricular relaxation was assessed by calculating the time relaxation constant, tau. Verapamil increased tau significantly only after beta adrenergic blockade, whereas nifedipine and dilazep reduced it both before and after beta adrenergic blockade. These data suggest that reflex beta adrenergic mechanisms may modulate the effects of calcium blockade on both systolic and diastolic performance.

Animals↗
PubMedDate not supplied

Renal vascular effects of dilazep antagonized by 3-isobutyl-1-methyl-xanthine.

The effects of different doses of dilazep on renal hemodynamics, urine formation, and renin release were studied in anesthetized dogs. Intrarenal arterial infusion of dilazep (1 microgram/kg/min) increased renal blood flow, with no change in systemic arterial blood pressure and renal venous plasma renin activity. Renal vasodilation induced by dilazep was completely inhibited by intrarenal arterial infusion of 3-isobutyl-1-methyl-xanthine (IBMX; 11.1 micrograms/kg/min), a potent adenosine receptor antagonist, but not by indomethacin (13 mg/kg i.v.). These results suggest that dilazep has a vasodilatory action in the kidney--one that is independent of the renal renin-angiotensin system. The inhibitory action of IBMX on the dilazep-induced renal vasodilation indicates that the renal vascular effects of dilazep may be exerted by augmentation of endogenous adenosine and mediated through adenosine receptors.

1-Methyl-3-isobutylxanthine↗