Effects of non-peptide angiotensin II-receptor antagonists on pentylenetetrazol kindling in mice

The effects of non-peptide AT1- and AT2-receptor antagonists DuP 753 (losartan) and PD 123319 on the intensity of pentylenetetrazol (PTZ)-kindled seizures in mice were studied. PTZ was injected intraperitoneally at a subconvulsive dose of 40 mg/kg at 48 h until the appearance of clonic seizures. DuP 753 administered intracerebroventricularly (i.c.v.) tended to decrease seizure intensity. Successive administration of ineffective doses of DuP 753 (losartan) and AT2 (angiotensin II) significantly decreased seizure intensity. PD 123319 (i.c.v.) decreased seizure intensity. Combination of ineffective doses of PD 123319 and AT2 also significantly decreased seizure intensity. The results suggest the role of AT2 receptor and its subtypes in PTZ-kindled seizures as well as an action of DuP 753 and PD 123319 similar to the action of AT2, an AT2-receptor agonist.