Gagnon G, Regoli D, Rioux F
Br J Pharmacol. 1980 Jul;69(3):389-96. doi: 10.1111/j.1476-5381.1980.tb07027.x.
1 The vasodilator effects of glucagon and adenosine cyclic 3',5'-monophosphate (cyclic AMP) were evaluated in strips of rabbit renal artery contracted with noradrenaline (NA) in the absence and presence of phosphodiesterase inhibitors or calcium (Ca(2+)) antagonists.2 The vascular relaxant effect of glucagon was markedly potentiated by various concentrations of four different phosphodiesterase inhibitors (papaverine, theophylline, 3-isobutyl-l-methylxanthine (IBMX) and indomethacin), while that of cyclic AMP was potentiated by only two of them (papaverine and indomethacin) and inhibited by the others (theophylline and IBMX).3 Amongst the four phosphodiesterase inhibitors, IBMX (10 mug/ml) was found to produce the largest potentiation (e.g. the sensitivity increased by a factor of 10) of glucagon-induced vascular relaxations (ED(50) of glucagon in the presence of IBMX = 9.2 +/- 1.0 ng/ml).4 Ca(2+) antagonists such as verapamil and SKF 525A produced a dose-dependent inhibition of the vasodilator action of glucagon. Verapamil (2.5 mug/ml) also antagonized cyclic AMP-induced vascular relaxations.5 The vasodilator effect of verapamil was inhibited dose-dependently by raising the concentration of extracellular Ca(2+) from 0.05 to 0.2 g/l (or 1.25 to 5.0 mM) while those elicited by glucagon or cyclic AMP were not influenced, thus suggesting that the latter two drugs do not interfere with Ca(2+) influx.6 Disodium edetate (Na(2)EDTA, 210 to 840 mug/l) produced a dose-dependent vasodilator effect which was attributed to the facilitation of Ca(2+) extrusion from the smooth muscle cells and/or Ca(2+) binding to the cell membrane. The relaxation produced by Na(2)EDTA was significantly blocked by verapamil (10 mug/ml) or SKF 525A (10 mug/ml).7 The results were taken as an indication that glucagon produces at least a fraction of its vasodilator effect by promoting Ca(2+) extrusion from the vascular smooth muscle cells and/or Ca(2+) binding to or sequestration into intracellular sites, presumably via a cyclic AMP-dependent mechanism.
在有无磷酸二酯酶抑制剂或钙（Ca(2+)）拮抗剂存在的情况下，研究了胰高血糖素和环磷腺苷（环磷酸腺苷）对用去甲肾上腺素（NA）收缩的兔肾动脉条的血管舒张作用。
四种不同的磷酸二酯酶抑制剂（罂粟碱、茶碱、3 -异丁基-1 -甲基黄嘌呤（IBMX）和吲哚美辛）的不同浓度均显著增强了胰高血糖素的血管舒张作用，而环磷酸腺苷的血管舒张作用仅被其中两种（罂粟碱和吲哚美辛）增强，被其他两种（茶碱和IBMX）抑制。
在四种磷酸二酯酶抑制剂中，发现IBMX（10微克/毫升）对胰高血糖素诱导的血管舒张作用产生最大的增强作用（例如，敏感性提高了10倍）（在存在IBMX的情况下，胰高血糖素的ED(50)=9.2±1.0纳克/毫升）。
维拉帕米和SKF 525A等Ca(2+)拮抗剂对胰高血糖素的血管舒张作用产生剂量依赖性抑制。维拉帕米（2.5微克/毫升）也拮抗环磷酸腺苷诱导的血管舒张。
将细胞外Ca(2+)浓度从0.05提高到0.2克/升（或1.25到5.0毫摩尔）时，维拉帕米的血管舒张作用受到剂量依赖性抑制，而胰高血糖素或环磷酸腺苷引起的血管舒张不受影响，这表明后两种药物不干扰Ca(2+)内流。
依地酸二钠（Na(2)EDTA，210至840微克/升）产生剂量依赖性血管舒张作用，这归因于促进Ca(2+)从平滑肌细胞挤出和/或Ca(2+)与细胞膜结合。维拉帕米（
