Relaxing effects of dilazep and lidoflazine in dog cerebral and renal arteries independent of adenosine.
The adenosine potentiating drugs dilazep and lidoflazine were studied for their relaxing ability in isolated dog cerebral and renal arteries contracted under conditions which induce the opening of potential-dependent calcium channels (using K+ at 30, 50 and 100 mmol/l) and under conditions which induce the opening of receptor-operated calcium channels (prostaglandin F2 alpha, PGF2 alpha; 5-hydroxytryptamine, 5-HT) and compared with those of adenosine and a standard calcium entry blocker, diltiazem. Dilazep, lidoflazine and diltiazem exerted concentration-dependent relaxation in cerebral and renal artery ring strips contracted with 30, 50 and 100 mmol/l K+. However, dilazep was slightly more potent at 100 mmol/l K+. In contrast, whereas the high concentration of adenosine (1 X 10(-5)-3.7 X 10(-4) mol/l) relaxes these arteries only at 30 mmol/l K+, it produced a more pronounced concentration-dependent relaxation when PGF2 alpha or 5-HT was used as a contracting agent. The order of relaxing responses of both cerebral and renal arterial ring strips contracted by PGF2 alpha were: diltiazem greater than adenosine greater than lidoflazine greater than dilazep. On the other hand, the relaxing responses on cerebral and renal arteries contracted with 5-HT were: diltiazem greater than lidoflazine greater than adenosine greater than dilazep and diltiazem greater than adenosine greater than lidoflazine greater than dilazep, respectively. Adenosine deaminase reversed the relaxation produced by adenosine, but was unable to reverse the relaxing responses to diltiazem, lidoflazine and dilazep. These findings suggest that dilazep and lidoflazine have a direct relaxing effect independent of adenosine in cerebral and renal artery ring strips possibly through their calcium entry blocking activity. The data suggest that adenosine is more effective on the receptor-operated contractions, whereas dilazep and lidoflazine are more effective on the potential-dependent contractions.
Mustafa
S J
SJ
Department of Pharmacology, School of Medicine, East Carolina University, Greenville, N.C.
Nakagawa
Y
Y
D000241:Adenosine / Q000502:physiology*; D000243:Adenosine Deaminase / Q000494:pharmacology; D000818:Animals; D001381:Azepines / Q000494:pharmacology*; D002536:Cerebral Arteries / Q000187:drug effects; D004109:Dilazep / Q000494:pharmacology*; D015237:Dinoprost / Q000494:pharmacology; D004285:Dogs; D005260:Female; D066298:In Vitro Techniques; D007537:Isometric Contraction / Q000187:drug effects; D008013:Lidoflazine / Q000494:pharmacology*; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D010879:Piperazines / Q000494:pharmacology*; D011188:Potassium / Q000494:pharmacology; D012077:Renal Artery / Q000187:drug effects; D012701:Serotonin / Q000494:pharmacology
D001381:Azepines; D010879:Piperazines; D012701:Serotonin; D015237:Dinoprost; D000243:Adenosine Deaminase; D004109:Dilazep; D008013:Lidoflazine; D000241:Adenosine; D011188:Potassium