Effects of manidipine and other calcium antagonists on rat renal arcuate arteries.
We investigated the effect of 1,4-dihydropyridine calcium antagonists (nifedipine, nisoldipine, and manidipine) on serotonin (5-hydroxytryptamine [5-HT])- and KCl (120 mmol/L)-induced contractions of rat isolated renal arcuate arteries. The preparation showed the well-known biphasic response to KCl-induced depolarization. All three calcium antagonists were more potent in inhibiting the second phase (tonic) compared with the first phase (transient) of the effect. The inhibitory concentration of 50% (pIC50) values were 6.92 +/- 0.24/8.51 +/- 0.08 (nifedipine, n = 32), 7.61 +/- 0.10/9.33 +/- 0.03 (nisoldipine, n = 28), and 7.61 +/- 0.13/9.07 +/- 0.06 (manidipine, n = 32) for the suppression of the first and second phases, respectively. In small coronary and renal arteries maximally activated with KCl solution, nifedipine and manidipine concentrations dependently inhibited the calcium concentration response curves. Manidipine was more potent than nifedipine (pIC50 coronary artery: 9.26 +/- 0.14 vs 7.93 +/- 0.22; pIC50 renal artery: 9.14 +/- 0.14 vs 7.77 +/- 0.21), but both compounds showed the same potency in the two different preparations. Furthermore, the influence of the calcium antagonists on the 5-HT concentration-response curve was investigated. Marked differences were found in the ability of the three compounds to inhibit the 5-HT-induced vasoconstriction of isolated renal arteries. For manidipine, a 93% +/- 3% reduction of the maximal 5-HT-induced contraction was observed, which was a significantly stronger inhibition compared with nifedipine (43% +/- 4.12%) or nisoldipine (26% +/- 0.37%). The pIC50 values were 7.96 +/- 0.15 (nifedipine), 8.17 +/- 0.14 (nisoldipine), and 7.84 +/- 0.12 (manidipine).(ABSTRACT TRUNCATED AT 250 WORDS)
Pfaffendorf
M
M
Department of Pharmacotherapy, University of Amsterdam, The Netherlands.
Mathy
M J
MJ
van Zwieten
P A
PA
D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D004095:Dihydropyridines / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D066298:In Vitro Techniques; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D009543:Nifedipine / Q000494:pharmacology; D015737:Nisoldipine / Q000494:pharmacology; D009578:Nitrobenzenes; D010879:Piperazines; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012077:Renal Artery / Q000187:drug effects*; D012701:Serotonin / Q000494:pharmacology
D002121:Calcium Channel Blockers; D004095:Dihydropyridines; D009578:Nitrobenzenes; D010879:Piperazines; D012701:Serotonin; D015737:Nisoldipine; D011189:Potassium Chloride; C054218:manidipine; D009543:Nifedipine