Abstract
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.
Published Version (Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.