INHIBITION BY (-)-CICLETANINE OF THE VASCULAR REACTIVITY TO ANGIOTENSIN-II AND VASOPRESSIN IN ISOLATED RAT VESSELS

In pithed rats, the levorotatory (-)-enantiomer of cicletanine reduces the presser responses to angiotensin II (AII) and also, to a lesser e xtent, those to arginine-vasopressin (AVP). Here we have attempted to characterize further these inhibitory effects by studies of isolated p erfused rat kidney and mesenteric vascular beds. In the isolated rat k idney, (-)-cicletanine behaves as a noncompetitive antagonist of AII-a nd AVP-receptor stimulation, with K-i values of 9.6 and 208 mu mol/L r espectively. In the isolated mesenteric vascular bed, (-)-cicletanine antagonized both AII dependent contractions with an inhibitory concent ration (IC50) of 54.0 +/- 20.5 mu mol/L (n = 6), and AVP dependent con tractions with an IC50 of 31.6 +/- 5.0 mu mol/L (n = 8). In conclusion , (-)-cicletanine antagonizes AII more effectively in rat kidney than in mesenteric vascular beds. Moreover, in rat kidney vascular beds (-) cicletanine is more potent in blocking the presser responses to AII th an in blocking those to AVP. A selective blockade of AII induced contr actions in kidney vascular beds can be one factor explaining both the greater antagonistic potency of (-)-cicletanine against AII compared w ith AVP in pithed rats, and the renal protective properties of cicleta nine in both hypertensive and aged rats. (C) 1998 American Journal of Hypertension, Ltd.