A comparative study on possible calcium antagonistic properties of indapamide and other drugs potentially interfering with calcium transport in isolated vascular smooth muscle.
In the present study the effects of indapamide (IN) were compared with those of chlorthalidone (C) and of drugs potentially interfering with calcium transport, e.g. verapamil (V), papaverine (P), phentolamine (PH) and diazoxide (D) using isolated rabbit aorta in order to detect calcium antagonistic properties. IN and C failed to show any relaxation effect towards either noradrenaline (NA)- or high K+-precontracted aorta strips, whereas V and P reduced the K+ contraction dose dependently and PH, V, P and D induced a significant relaxation of the NA contraction. Preincubation with IN or C did not affect the dose-response curve of NA-induced contractions. PH antagonized the NA contraction strongly whereas V and P shifted the dose-response curve to the right only at the highest concentration. In a Ca2+-depleted and high K+-depolarized aorta preincubation with V was able to antagonize Ca2+-induced contraction effectively in a dose-dependent fashion whereas P only showed partial inhibition at the highest concentration. The effects of the drugs on responses to NA in a Ca2+-free medium were also investigated. This type of contraction is likely to be due to mobilization of internally located Ca2+. The results demonstrate that PH was able to counteract this type of contraction effectively whereas only a high concentration of V, P and D was effective in reducing the Na contraction in Ca2+-free medium. Both IN and C failed to affect this type of contraction. In conclusion, the present results indicate that neither IN nor C possess calcium entry and or intracellular calcium antagonistic properties under different conditions as measured in a conduit vessel of rabbits. Moreover, the results point to an additional site of calcium antagonistic action for V, P and D, especially at higher concentrations.
D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects; D002121:Calcium Channel Blockers; D002122:Calcium Chloride / Q000494:pharmacology; D002752:Chlorthalidone / Q000494:pharmacology; D004232:Diuretics / Q000494:pharmacology*; D005260:Female; D066298:In Vitro Techniques; D007190:Indapamide / Q000494:pharmacology*; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism; D009638:Norepinephrine / Q000037:antagonists & inhibitors / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D011817:Rabbits; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology
D002121:Calcium Channel Blockers; D004232:Diuretics; D014665:Vasodilator Agents; D007190:Indapamide; D002122:Calcium Chloride; D002752:Chlorthalidone; D011188:Potassium; D009638:Norepinephrine