Effect of Amlodipine in Comparison to Nifedipine on Vascular Perfusion Pressure of Isolated Rat Kidney

Document Type : Original Article

Authors

1 Department of Biology, Kazeroon Branch, Islamic Azad University, Kazeroon, Iran

2 Razi Institute for Drug Research, Iran University of Medical Sciences, Tehran, Iran

3 Department of Physiology, Faculty of Veterinary Medicine, Tehran University, Tehran, Iran

Abstract

Objective(s)
This study aimed to investigate and to compare the effects of nifedipine and amlodipine, dihydropyridine (DHP) calcium channel blockers (CCBs) on perfusion pressure of isolated perfused rat kidney.
Materials and Methods
Following the establishment of renal perfusion with a constant baseline pressure of 85-95 mmHg, the renal vasculature was constricted by phenylephrine (PE) injection. Changes in the baseline perfusion pressure were recorded. Then nifedipine and amlodipine prepared in perfusion medium was fed to the kidney for 30 min. Finally alterations in the baseline pressure arising from PE administrations in the presence of CCBs were recorded and data analyses were done.
Results
PE-induced increases in perfusion pressure attenuated significantly in the presence of 5 and 10 pM of nifedipine and 1, 5, and 10 pM of amlodipine. Increases in perfusion pressure arising from PE (100 and 200 pM) in the presence of amlodipine (1, 5, and 10 pM) was significantly less than that in the presence of nifedipine (1, 5, and 10 pM). Calculated EC50 value of amlodipine for inhibition was significantly lower than that of nifedipine. Based on the EC50 values, the potency of amlodipine in inhibiting PE-induced responses is significantly higher compared to nifedipine.
Conclusion
The potency of amlodipine in inhibiting PE-induced increments in renal perfusion pressure is significantly higher compared to nifedipine.

Keywords


1.Weiner DA. Calcium-channel blockers. Med Clin North Am 1988; 72:83-115.
2.Parmley WW. Calcium antagonists in the prevention of atherosclerosis. In: Messerli FH editors. Cardiovascular Drug Therapy. W B Saunders Co; 1996. p. 901-907.
3.Reams GP. Do calcium channel blockers have renal protective effects?. Drugs Aging 1994; 4:263-287.
4.Hayashi K, Ozawa Y, Fujiwara K, Wakino S, Kumagai H, Saruta T. Role of action of calcium antagonists on efferent arterioles-with special references to glomerular hypertension. Am J Nephrol 2003; 23:229-244.
5.Mahmoudian M, Mirkhani H, Nehardani Z, Ghiaee S. Synthesis and biological activity of two new calcium channel blocker, mebudipine and dibudipine. J Pharm Pharmacol 1997; 49:1229-1233.
6.Zhang J, Berra-Romani R, Sinnegger-Brauns MJ, Striessnig J,Blaustein MP,Matteson DR. Role of Cav1.2 L- type Ca2+ channels in vascular tone: effects of nifedipine and Mg2+. Am J Physiol Heart Circ Physiol 2007; 292:H415-H425.
7.Van Zwieten PA, Pfaffendorf M. Pharmacology of the dihydropyridine calcium antagonists: relationship between lipophilicity and pharmacodynamic responses. J Hypertens 1993; 11: S3-S8.
8.Borchard U. Calcium antagonists in comparison:view of the pharmacologist. J Cardiovasc Pharmacol 1994; 24:S85-S91.
9.Roden DM. Antiarrhythmic drugs. In: Hardman JG, Limberd LE, Molinoff PB, Ruddon RW,Goodman A.editors.Goodman and Gilman’s The pharmacological basis of therapeutics. McGraw-Hill TX; 2001.p.933-967.
10.Hughes AD, Wijetunge S. The action of amlodipine on voltage-operated calcium channels in vascular smooth muscle. Br J Pharmacol 1993; 109:120-125.
11.Burges RA, Dodd MG. Amlodipine. Cardiovasc Drug Rev 1990; 8:25-44.
12.Hirano Y, Orikabe M, Hiraoka M. Effect of amlodipine on unitary non-L-type high voltage-activated Ca2+ channel currents in differentiated PC12 cells. Naunyn Schmiedebergs Arch Pharmacol 2001; 364:333-342.
13.Loutzenhiser R, Epstein M. Renal hemodynamic effects of calcium antagonists. In: Epstein M, Loutzenhiser R editors. Calcium Antagonists and the Kidney. Philadelphia:Hanley & Belfus;1990.p.33-74.
14.Loutzenhiser R, Epstein M, Horton C, Sonke P. Reversal by the calcium antagonist nisoldipine of norepinephrine-induced reduction of GFR:Evidence for preferential antagonism of preglomerular vasoconstriction. J Pharmacol Exp Ther 1985; 232:382-387.
15.Loutzenhiser R, Epstein M, Fischetti F, Horton C. Effects of amlodipine on renal hemodynamics. Am J Cardiol 1989; 64:122I-127I.
16.Loutzenhiser R, Horton C, Epstein M. Effects of diltiazem and manganese on renal hemodynamics: Studies in the isolated perfused rat kidney. Nephron 1985; 39:382-388.
17.Ebrahimi SA, Rouzrokh A. An improve method for injection of bolus doses of drugs into the perfusion circuit of isolated perfused rat kidney utilizing a six-port injection valve. Iran J Pharm Ther 2003; 2:12-14. 
18.Rouzrokh A, Ebrahimi SA, Rahbar-roshandel N, Mahmoudian M. Effect of mebudipine and dibudipine, two new calcium channel blockers on voltage-activated calcium currents of PC12 cells. Acta Physiol Hun 2007; 94:199-207.
19.Triggle DJ. The pharmacology of ion channels: with particular reference to voltage-gated Ca2+ channels. Eur J Pharmacol 1999; 375:311-325.
20.Striessnig J. Structural basis of drug binding to L Ca2+ channels. Trends Pharmacol Sci 1998; 19:108-15.
21.Mirkhani H, Dirin M, Youssef-Zayeh I. Mechanism of vasoselective action of mebudipine, a new calcium channel blocker. Vasc Pharmacol 2005; 42:23-29.
22.Hayashi K, Nagahama T, Oka K, Epstein M, Saruta T. Disparate effects of calcium antagonists on renal microcirculation. Hypertens Res 1996; 19:31-36.
23.Carmines PK, Fower BC, Bell PD. Segmental distinct effects of depolarization on intracellular [Ca2+] in renal arterioles. Am J Physiol 1993; 265: F677-F685.
24.Hansen PB, Jensen BL, Andreasen D, Skott O. Differential expression of T- and L-type voltage-dependent calcium channels in renal resistance vessels. Circ Res 2001; 89: 630-638.
25.Xu B, Xiao-hong L, Lin G, Queen L, Ferro A. Amlodipine, but not verapamil or nifedipine, dilates rabbit femoral artery largely through a nitric oxide- and kinin-dependent mechanism. _Br J Pharmacol 2002; 136:375-382.
26.Nayler W, Gu XH. The binding of amlodipine to its receptor. J Cardiovasc Pharmacol 1992; 20: S14-S16.
27.Vaghy P. Modulated multisubsite receptors for calcium channel ligands: unique binding of amlodipine. J Cardiovasc Pharmacol 1992; 20:S17-S24.
28.Furukawa T, Nukada T, Suzuki K, Fujita Y, Mori Y, Nishimura M, et al. Voltage and pH dependent block of cloned N-type Ca2+ channels by amlodipine. Br J Pharmacol 1997; 121: 1136-1140.
29.Kimura K, Suzuki N, Ohba S, Mise N, Miyashita K, Tojo A, et al. Effects of amlodipine, a calcium channel blocker, on rat renal arterioles. Ther Res 1997; 58:375-380.
30.Zhang H, Hintze TH. Amlodipine releases nitric oxide from canine coronary microvessels: an unexpected mechanism of action of a calcium channel-blocking agent. Circulation 1998; 97:576-580.
31.Zhang XP, Loke KE, Mital S, Chahwala S, Hintze TH. Paradoxical release of nitric oxide by an L-type calcium channel antagonist, the r+ enantiomer of amlodipine. J Cardiovasc Pharmacol 2002; 39:208-214.