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 micromol/L respectively. In the isolated mesenteric vascular bed, (-)-cicletanine antagonized both AII dependent contractions with an inhibitory concentration (IC50) of 54.0 +/- 20.5 micromol/L (n = 6), and AVP dependent contractions with an IC50 of 31.6 +/- 5.0 micromol/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.
Vargas
F
F
Department of Physiology (FV), School of Medicine of Granada, Spain.
Alvarez-Guerra
M
M
Droy-Lefaix
M T
MT
Garay
R P
RP
D000804:Angiotensin II / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001127:Arginine Vasopressin / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D011725:Pyridines / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012079:Renal Circulation / Q000187:drug effects*; D013152:Splanchnic Circulation / Q000187:drug effects*; D013237:Stereoisomerism
D000959:Antihypertensive Agents; D011725:Pyridines; D000804:Angiotensin II; D001127:Arginine Vasopressin; C038068:cicletanine