Disease relevance of Efonidipine

• In contrast to older calcium channel antagonists, the newer DHPs, manidipine, nilvadipine, benidipine and efonidipine, dilate not only afferent but also efferent renal arterioles, a potentially beneficial effect that may improve glomerular hypertension and provide renoprotection [1].
• Of interest, efonidipine decreased proteinuria in proteinuric patients who failed to manifest decreases in systemic BP [2].
• Finally, the incidence of adverse effects, including hyperkalemia and cough, was less in the efonidipine-treated group.Both efonidipine and ACE inhibitors preserved renal function in hypertensive patients with renal impairment [2].
• Thus, the calcium antagonist efonidipine seems to play an important role in the regulation of apoptosis and proliferation of glomerular cells and may be effective in preventing nephrosclerosis exacerbated by NOS inhibition [3].
• Effects of efonidipine on platelet and monocyte activation markers in hypertensive patients with and without type 2 diabetes mellitus [4].

High impact information on Efonidipine

• In contrast, efonidipine caused a similar magnitude of vasodilatation (16 +/- 4%) compared with 18 +/- 2%; n = 6), and mibefradil caused greater dilatation of efferent arterioles (20 +/- 4%, n = 7) than that of afferent arterioles (13 +/- 4%) [5].
• To address these issues, the effects of efonidipine and its R(-)- and S(+)-isomers on these Ca(2+) channel subtypes were examined electrophysiologically in the expression systems using Xenopus oocytes and baby hamster kidney cells (BHK tk-ts13) [6].
• These antagonists exerted contrasting actions on the filtration fraction (FF), with an increase being elicited by nifedipine, whereas efonidipine had no effect [7].
• In the sino-atrial node, 1 microM efonidipine produced increase in cycle length accompanied by prolongation of the phase 4 depolarization which was not prominent with 0.1 microM nifedipine [8].
• All Ca2+ channel antagonists except efonidipine shifted the maximum diastolic potential to the positive direction, decreased the action potential amplitude and prolonged the action potential duration [9].

Chemical compound and disease context of Efonidipine

• To compare the antianginal effects of 1,4-dihydropyridine-type calcium-channel blockers, we evaluated the effects of benidipine, amlodipine, nifedipine, and efonidipine on vasopressin-induced myocardial ischemia in rats, an experimental model of angina [10].

Biological context of Efonidipine

• A characteristic feature of efonidipine was selective suppression of the later phase of pacemaker depolarization with no effect on action potential amplitude and duration [9].
• Finally, in patients with chronic renal disease, a 48-week treatment with efonidipine reduced proteinuria, and this effect was seen even when the mean arterial blood pressure failed to reach below 100 mm Hg [11].
• At 10(-6) M, efonidipine completely inhibited the afferent (A-II, 89 +/- 7% reversal; NE, 99 +/- 8% reversal) and efferent arteriolar vasoconstriction (A-II, 93 +/- 4% reversal; NE, 87 +/- 9% reversal) [12].
• 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 [13].
• These findings suggest that administration of efonidipine to hypertension patients with diabetes may prevent the development of cardiovascular complications caused by cell adhesion molecules or activated platelets and monocytes [4].

Anatomical context of Efonidipine

• Effects of Ca2+ channel antagonists on sinus node: prolongation of late phase 4 depolarization by efonidipine [9].
• The voltage-dependent non-selective cation channel sensitive to the L-type calcium channel blocker efonidipine regulates Ca2+ influx in brain vascular smooth muscle cells [14].
• The cholesteryl ester content in the macrophages was increased by incubation with beta-VLDL, and the increase was inhibited by efonidipine [15].
• It is possible that flunarizine and efonidipine could directly interact with mitochondrial membrane [16].
• In the present study, we examined the frequency dependence of efonidipine action on the T-type Ca2+ channel in isolated guinea-pig ventricular myocytes [17].

Associations of Efonidipine with other chemical compounds

• The effects of efonidipine, a 1,4-dihydropyridine phosphonate, and structurally related compounds on rabbit sino-atrial node action potential were examined with microelectrodes [18].
• In a previous in vitro study, we clarified that efonidipine dramatically suppresses aldosterone secretion from human adrenocortical tumor cells during angiotensin II (Ang II)- and K+-stimulation, whereas nifedipine, a dominant L-type Ca2+ channel antagonist, does not [19].
• Possible requirement of phosphonate moiety for efonidipine effects on the sino-atrial node action potential [18].
• Furthermore, efonidipine increased the intracellular cyclic AMP content in J774 macrophages [15].
• 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 [20].

Gene context of Efonidipine

• Neither of these inhibitors suppressed the efonidipine-induced ABCA1 protein expression [21].
• Pretreatment with efonidipine attenuated the decrease in CBF induced by ET-1 significantly and dose-dependently [22].
• 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%) [13].
• These findings suggest that efonidipine acts via T-type Ca2+ channel blockade to significantly reduce aldosterone secretion, and that this effect is mediated, at least in part, by suppression of 11-beta-hydroxylase and aldosterone synthase expression [23].
• Efonidipine decreased plasma aldosterone concentration despite the increase in plasma renin activity and Ang II, suggesting that T-type Ca2+ channels may also play an essential role in the secretion of aldosterone in healthy human volunteers [19].

Analytical, diagnostic and therapeutic context of Efonidipine

• Efonidipine (0.33 mg/kg per min, n = 9), however, had no effect on filtration fraction, with 14 +/- 6% increments in RPF (P < 0.05) and 14 +/- 7% increments in GFR (P = 0.08) [5].
• 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 [13].
• The levels of urinary albumin in the diabetic SHRs after treatment with efonidipine were significantly less than those in the diabetic SHRs at 8 and 12 weeks (P < 0.01) [24].

References