Effects Of Efonidipine Hydrochloride Research Articles

Effect of Efonidipine Hydrochloride in a Dog that Showed Severe Clinical Symptoms Following Atrial Fibrillation

Effect of Efonidipine Hydrochloride in a Dog that Showed Severe Clinical Symptoms Following Atrial Fibrillation

Effects of Efonidipine Hydrochloride on Heart Rate and Circulatory Changes Due to Stress

Efonidipine hydrochloride is a dual Ca channel blocker that inhibits T-type Ca channels, which are localized in the sinoatrial node and are involved in the pacemaker mechanism of the heart, as well as L-type Ca channels. In the present study, the effect of efonidipine hydrochloride in inhibiting an increase in heart rate along with changes in circulation during mental and physical stress was examined using normotensive volunteers. A mental arithmetic test caused significant increases in heart rate and blood pressure, which were significantly inhibited 3 hours after oral administration of 40 mg of efonidipine hydrochloride but not at 1 week after cessation of administration. In contrast, the plasma norepinephrine, epinephrine, renin activity, and aldosterone levels following the test were unchanged at both 3 hours and 1 week after administration of efonidipine hydrochloride. Physical stress in the form of cold by immersing one hand in ice water for 2 minutes induced similar increases in the heart rate and blood pressure, which were significantly reduced at 3 hours but not at 1 week after administration of efonidipine hydrochloride. The plasma levels of the humoral factors previously described following the physical stress were unchanged at either 3 hours or 1 week after administration of efonidipine hydrochloride. These results suggest that efonidipine hydrochloride inhibits increases in heart rate and blood pressure due to stress, presumably by blocking T-type Ca channels rather than by inhibiting the sympathetic nervous system. Therefore, efonidipine hydrochloride is expected to be a Ca antagonist that exhibits a strong cardioprotective effect.

The effect of efonidipine hydrochloride on human subcutaneous microvascular constrictor responses

The effect of efonidipine hydrochloride on human subcutaneous microvascular constrictor responses

Effects of efonidipine hydrochloride on renal arteriolar diameters in spontaneously hypertensive rats.

Efonidipine, a calcium antagonist, has been reported to dilate not only afferent but also efferent arterioles, thereby reducing glomerular hydrostatic pressure. We investigated the effect of chronic treatment with efonidipine or lisinopril on the afferent and efferent arteriolar diameters by the vascular cast technique. Four-week-old spontaneously hypertensive rats (SHR) were divided into three groups: untreated, efonidipine (25 mg/kg/day)-treated, and lisinopril (3 mg/kg/day)-treated. At 22 weeks of age, the renal vasculatures were fixed at the maximally dilated condition. The morphometrical measurements showed that the treatments with efonidipine and lisinopril caused structural alteration of the vasculature, resulting in significantly greater efferent arteriolar diameters than in untreated SHR. In addition, lisinopril-treated rats had wider afferent lumina. The renoprotective effect of efonidipine and lisinopril might be partly due to the structurally larger efferent arteriolar lumen.

Renal effects of efonidipine hydrochloride, a new calcium antagonist, in spontaneously hypertensive rats with glomerular injury.

1. To obtain some insight into the renoprotective mechanism of the new calcium antagonist efonidipine hydrochloride, we evaluated the acute effects of efonidipine on proteinuria, glomerular haemodynamics and the tubuloglomerular feedback (TGF) mechanism in anaesthetized 24-25-week-old spontaneously hypertensive rats (SHR) with glomerular injury. 2. Efonidipine infusion at 10 micrograms/kg per h following a bolus dose of 10 micrograms/kg, i.v., reduced systemic blood pressure (BP) and renal vascular resistance, whereas renal plasma flow (RPF), glomerular filtration rate (GFR), filtration fraction, urine volume and urinary sodium excretion were unaltered. Urinary protein excretion was clearly diminished from 163 +/- 25 to 105 +/- 24 ng/min per g kidney weight. 3. Micropuncture experiments revealed that the maximal reduction of proximal stop-flow pressure (SFP), an index of glomerular capillary pressure (Pgc), induced by loop of Henle perfusion was significantly less with efonidipine treatment (6.7 +/- 1.0% of SFP with no loop flow) than in control (23.8 +/- 3.1%). In the presence of efonidipine, SFP at half-maximal reduction (SFP1/2max), which approximates Pgc at the in vivo steady state tubular flow rate, remained unchanged compared with control (36.9 +/- 0.8 vs 35.3 +/- 0.7 mmHg, respectively) and the slope of dependency on mean BP was not different between control and efonidipine. 4. These results indicate that efonidipine attenuates the TGF response in SHR by dilating the afferent arteriole, thus maintaining the level of RPF and GFR despite reduced renal perfusion pressure. Constant GFR and SFP1/2max under efonidipine suggest that single nephron GFR and Pgc remain unaltered and that a marked reduction in proteinuria is achieved without changes in single nephron GFR or Pgc of superficial nephrons.

P-1014 - Effects of efonidipine hydrochloride (NZ-105), a dihydropyridine derivative with calcium antagonistic action, on acute myocardial ischemia in anesthetized open-chest dogs.

P-1014 - Effects of efonidipine hydrochloride (NZ-105), a dihydropyridine derivative with calcium antagonistic action, on acute myocardial ischemia in anesthetized open-chest dogs.

P-1013 - Effect of efonidipine hydrochloride (NZ-105), a dihydropyridine derivative with calcium antagonistic action, on myocardial oxygen tension in anesthetized dogs.

P-1013 - Effect of efonidipine hydrochloride (NZ-105), a dihydropyridine derivative with calcium antagonistic action, on myocardial oxygen tension in anesthetized dogs.

Effects of efonidipine hydrochloride, a calcium antagonist derived from dihydropyridine, on acute myocardial ischemia in anesthetized open-chest dogs

Effects of efonidipine hydrochloride (NZ-105), a dihydropyridine calcium antagonist, on the cardiovascular system were studied in dogs, in which the left anterior descending coronary artery (LAD) was ligated for 50 min. NZ-105 (10 or 30 micrograms/kg), nifedipine (NIF, 1 or 3 micrograms/kg) or nisoldipine (NIS, 1 or 3 micrograms/kg) was injected i.v. before LAD ligation. NZ-105, NIS or NIF decreased the total peripheral resistance (TPR) and blood pressure (BP) and increased the cardiac output (CO) and regional myocardial blood flow (RBF) dose-dependently. LAD ligation decreased RBF and produced segmental bulging in the ischemic area, decreased BP and CO, and did not change TPR. NZ-105, NIF or NIS attenuated the LAD ligation-induced regional myocardial changes. During LAD ligation, in the presence of NZ-105 (30 micrograms/kg), the values of heart rate (HR), BP, and TPR were lower, and that of CO was higher than those in the absence of the drug. Similar results were obtained with NIS (3 micrograms/kg) except that the value of HR in the presence of NIS was not lower. During ischemia, the presence of NIF (3 micrograms/kg), did not significantly change the values of the systemic circulation from those observed in the absence of NIF. In conclusion, NZ-105 may exert a cardioprotective effect by decreasing the oxygen demand of the ischemic heart.

Effect of efonidipine hydrochloride (NZ-105), a dihydropyridine derivative with calcium antagonistic action, on myocardial oxygen tension in anesthetized dogs

Effect of efonidipine hydrochloride (efonidipine) on myocardial oxygen tension (PO2) was investigated in open-chest anesthetized dog and compared with those of nifedipine and nisoldipine. PO2 was measured by a membrane-coated platinum wire, which was inserted into the myocardium. Intravenous administration of efonidipine (10 and 30 micrograms/kg) decreased mean blood pressure to a similar extent to that induced by nifedipine (1 and 3 micrograms/kg) or nisoldipine (1 and 3 micrograms/kg). Efonidipine increased coronary blood flow (CBF) and decreased the double product (DP) dose-dependently. Similar results were observed in nisoldipine-treated animals. Nifedipine produced a transient increase in CBF and a transient decrease in DP. The duration of action of efonidipine on CBF was longer than that of nifedipine or nisoldipine. Efonidipine increased PO2, and the effect was more pronounced in the endocardial region than in the epicardial region. Nifedipine had no significant effect on the PO2, while nisoldipine significantly increased PO2 in the endocardial region. The effect of efonidipine on the PO2 was greater than that of nisoldipine and the duration of action of efonidipine was longer than that of nisoldipine. These results suggest that efonidipine may increase PO2 by mediating, at least in part, a long-lasting increase in oxygen supply and a decrease in oxygen demand in dog heart.

Effects of efonidipine hydrochloride (NZ-105), a calcium antagonist, on renal function in conscious spontaneously hypertensive rats

1. 1. We investigated the effects of short- and long-term administration of efonidipine hydrochloride (NZ-105), 1,4-dihydropyridine derivative, in conscious spontaneously hypertensive rats (SHR). 2. 2. Oral administration of NZ-105 for 12 weeks caused diuretic and natriuretic effects, which were not attenuated during the experimental period. 3. 3. In the short-term experiment for investigating the mechanism of the diuretic effect, intravenous injection of NZ-105 (0.03 mg/kg of body weight) significantly increased the urine volume (UV), renal plasma flow (RPF) and glomerular filtration rate (GFR). The increment rate of UV and RPF was 105.4 ± 17.8% and 111.7 ± 72.8%, respectively, which were larger than the increment rate of GFR (38.5 ± 14.0%). 4. 4. The diuretic or natriuretic effect of NZ-105 was suggested to be due to both the inhibition of sodium reabsorption and, at least in part, the increase of GFR.

Effects of Efonidipine Hydrochloride on Cholesterol Estérification Mediated by Beta-Very Low Density Lipoprotein in J774 Macrophages

The effects of efonidipine hydrochloride (efonidipine), a dihydropyridine calcium antagonist, on the cholesterol ester metabolism induced by beta-migrating very low density lipoprotein (β-VLDL) in J774 macrophages were studied. The cholesteryl ester content in the macrophages was increased by incubation with β-VLDL, and the increase was inhibited by efonidipine. Oleic acid incorporation into cellular cholesteryl ester was increased by β-VLDL in J774 macrophages. The incorporation at an early phase of β-VLDL induction (0-3 hr) was inhibited by efonidipine. This inhibitory effect of efonidipine was greater at an early phase of β-VLDL induction (0–3 hr) than at a late phase of the induction (8–11 hr). Pretreatment of the cells with efonidipine enhanced the inhibitory effect. Efonidipine also inhibited β-VLDL degradation but not the binding and association in macrophages without pretreatment. β-VLDL binding and association to macrophages were decreased by pretreatment of the cells with efonidipine. β-VLDL metabolism was also decreased by dibutyryl cyclic AMP pretreatment. The decrease of β-VLDL metabolism by efonidipine was prevented by co-treatment with efonidipine and HA1004, a protein kinase A inhibitor. Furthermore, efonidipine increased the intracellular cyclic AMP content in J774 macrophages. These findings suggest that efonidipine suppresses cholesterol ester deposition in atherosclerotic foam cells by inhibiting the modified lipoprotein metabolism and cholesterol esterification mainly through elevation of the cellular cyclic AMP level.