Will chronic intracerebroventricular saralasin infusion produce selective blockade of brain angiotensin II receptors in the rat?
In an attempt to produce chronic, selective, pharmacological blockade of brain angiotensin II (AII) receptors, we infused saralasin (1sar, 8ala-angiotensin II), a competitive AII receptor antagonist, into the cerebral ventricles of rats for 5 days. We found that i.c.v. saralasin infusion at a dose of 12 micrograms/hr selectively blocked brain AII receptors, as determined by pressor responses to acute i.c.v. and i.v. AII. Infusion of this dose of saralasin in rats maintained on a high sodium intake produced a pressor response that was not seen in rats maintained on a normal sodium intake. The cardiovascular responses to chronic i.c.v. saralasin were similar to those seen in response to chronic i.c.v. AII, suggesting that i.c.v. saralasin acts as an agonist at central AII receptors in rats maintained on a high sodium intake. The apparent agonistic activity of saralasin may limit its usefulness in assessing the physiological role of the central effects of AII.
D000804:Angiotensin II / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000502:physiology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001921:Brain / Q000187:drug effects*; D002552:Cerebral Ventricles; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D011945:Receptors, Angiotensin / Q000187:drug effects*; D011956:Receptors, Cell Surface / Q000187:drug effects*; D012504:Saralasin / Q000008:administration & dosage* / Q000494:pharmacology; D012964:Sodium / Q000494:pharmacology; D014882:Water-Electrolyte Balance / Q000187:drug effects
D011945:Receptors, Angiotensin; D011956:Receptors, Cell Surface; D000804:Angiotensin II; D012964:Sodium; D012504:Saralasin