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 pressor responses to angiotensin II (AII) and also, to a lesser extent, those to arginine-vasopressin (AVP). Here we have attempted to characterize further these inhibitory effects by studies of isolated perfused rat kidney and mesenteric vascular beds. In the isolated rat kidney, (−)-cicletanine behaves as a noncompetitive antagonist of AII- and AVP-receptor stimulation, with Ki values of 9.6 and 208 μmol/L respectively. In the isolated mesenteric vascular bed, (−)-cicletanine antagonized both AII dependent contractions with an inhibitory concentration (IC50) of 54.0 ± 20.5 μmol/L (n = 6), and AVP dependent contractions with an IC50 of 31.6 ± 5.0 μmol/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 pressor responses to AII than in blocking those to AVP. A selective blockade of AII induced contractions in kidney vascular beds can be one factor explaining both the greater antagonistic potency of (−)-cicletanine against AII compared with AVP in pithed rats, and the renal protective properties of cicletanine in both hypertensive and aged rats.