Effects of the divalent cations nickel and cadmium on contractions of rat aorta to endothelin-1.
1. The effects of inorganic and organic calcium channel antagonists on the contractile responses of rat isolated aortic rings to endothelin-1 (ET-1) were studied. 2. ET-1 (0.1-100 nM) evoked concentration-related contractile responses of the rat aorta (EC50 1.65 +/- 0.22 nM, Emax 125.8 +/- 4.5 %KClmax, n = 20). In Ca(2+)-free modified Krebs solution (containing 1 mM EGTA) aortic rings failed to contract to ET-1 (0.1-30 nM). 3. Nickel chloride (0.2-0.8 mM) attenuated the ET-1 (1-100 nM)-induced contraction of rat aorta (response (%KClmax) to 10 nM ET-1: control 132.0 +/- 8.7 and after 0.2 mM Ni2+ 90.3 +/- 14.8, 0.4 mM Ni2+ 54.7 +/- 12.3, 0.8 mM Ni2+ 10.3 +/- 4.4, n = 6/group). Cadmium chloride (10-30 microM) depressed the maxima of the concentration-response curves to ET-1 with an IC50 of 15.4 +/- 1.5 microM (n = 6). 4. The ET-1 evoked contractile responses were not modified by the dihydropyridine calcium channel antagonist, nicardipine (0.1 microM), or by omega-conotoxin (1.0 microM). Cinnarizine (10 microM), however, significantly attenuated the maximum response to ET-1 (96.9 +/- 6.0 vs 128.0 +/- 5.8 %KClmax for control), but failed to modify the EC50 value. 5. Amiloride, a Na(+)-Ca2+ exchange inhibitor, also depressed the maxima of the concentration-response curves to ET-1 with an IC50 of 0.45 +/- 0.05 mM (n = 4).(ABSTRACT TRUNCATED AT 250 WORDS)
Lawson
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Sanofi Research Center, Brussels, Belgium.
Chatelain
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D000584:Amiloride / Q000494:pharmacology; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects*; D002104:Cadmium / Q000494:pharmacology*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D016232:Endothelins / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D009532:Nickel / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D014661:Vasoconstriction / Q000187:drug effects*
D002121:Calcium Channel Blockers; D016232:Endothelins; D002104:Cadmium; D000584:Amiloride; D009532:Nickel