VASORELAXANT EFFECTS OF CICLETANINE AND ITS (- AND (-)-ENANTIOMERS INISOLATED HUMAN PULMONARY-ARTERIES())

The purpose of the study was to investigate, in isolated human pulmona ry artery, the ability of cicletanine and its (-) and (+)-enantiomers to attenuate the endothelin-1 (Et-1) induced vasoconstriction, and to potentiate vasorelaxation (relative to plateau of the effect of Et-1) by sodium nitroprusside (SNP) and human atrial natriuretic peptide (AN P). In pulmonary artery rings, Et-1 induced a concentration-dependent vasoconstriction with median effective concentration (EC50 = 26 +/- 2. 8 nmol/L, Pretreatment of the vessels with 100 mu mol/L (+/-)-cicletan ine reduced the effect of Et-1 (EC50 = 36 +/- 3.5 nmol/L; P <.01), (-) -enantiomer displayed greater capacity to antagonize the vasoconstrict or action of Et-1 (EC50 = 47 +/- 4.2 nmol/L) v (+)-enantiomer (EC50 - 29.9 +/- 6.5 nmol/L; P <.01). In arterial rings, precontracted with 10 nmol/L Et-1, ANP caused vasorelaxation (EC50 = 9.7 +/- 1.9 nmol/L). T he relaxant effect of ANP was potentiated by 100 mu mol/L of (-)-(EC50 = 4.2 +/- 0.6 nmol/L; P <.01), but not (+)-cicletanine (EC50 = 7.6 +/ - 0.7 nmol/L). Sodium nitroprusside relaxed pulmonary artery rings pre contracted with 10 nmol/L. Et-1 (EC50 = 41 +/- 11 nmol/L). The effect of SNP was potentiated by 10 mu mol/L (rt)-cicletanine (EC,, = 9.0 +/- 0.7 nmol/L; P <.05), The potentiating effect of 10 mu mol/L (+)-cicle tanine was weaker (EC50 = 7.9 +/- 1.8 nmol/L) than that of (-)-enantio mer (EC50 = 3.3 +/- 0.54 nmol/L; P <.05), The relaxant effect of SNP w as not further potentiated by 100 mu mol/L (+/-)-cicletanine. The pres ent results demonstrate that, cicletanine antagonizes Et-1 induced vas oconstriction in an isolated human pulmonary artery and potentiates va sorelaxation by two guanylate cyclase activators, ANP and SNF. (-)-Cic letanine displays greater vasorelaxant activity v (+)-enantiomer. (C) 1998 American Journal of Hypertension, Ltd.