Inhibition by (−)-Cicletanine of the Vascular Reactivity to Angiotensin II and Vasopressin in Isolated Rat Vessels

• Published in: American journal of hypertension 1998-05, Vol.11 (5), p.579-584
• Main Authors: Vargas, Félix, Alvarez-Guerra, Miriam, Droy-Lefaix, Marie-Thérèse, Garay, Ricardo P
• Format: Article
• Language: English
• Subjects: angiotensin II; Angiotensin II - antagonists & inhibitors; Angiotensin II - pharmacology; Animals; Antihypertensive agents; Antihypertensive Agents - pharmacology; Arginine Vasopressin - antagonists & inhibitors; Arginine Vasopressin - pharmacology; Biological and medical sciences; Cardiovascular system; Cicletanine; In Vitro Techniques; Male; Medical sciences; Pharmacology. Drug treatments; Pyridines - pharmacology; rat; Rats; Rats, Wistar; Renal Circulation - drug effects; Splanchnic Circulation - drug effects; Stereoisomerism; vascular smooth muscle; vasopressin; vessels
• ISSN: 0895-7061; 1879-1905; 1941-7225
• DOI: 10.1016/S0895-7061(97)00407-X

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 K i 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 (IC 50) of 54.0 ± 20.5 μmol/L (n = 6), and AVP dependent contractions with an IC 50 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.