ABSTRACT
Our previous studies revealed that Angiotensin (Ang) II has anticonvulsant effects in acute seizure models. However, data on its role in experimental models of epilepsy are missing. In the present study, we tested whether posttreatment with Ang II after kainate (KA)-induced status epilepticus (SE) can affect epileptogenesis, concomitant behavioral changes, and brain damage. The Wistar rats were intracerebroventricularly infused via osmotic mini-pumps with Ang II (1.52µg/µl/day for 28days) after SE. Spontaneous motor seizures (SMS) were video-recorded for up to three months. Locomotor activity, anxiety, and depression-like behavior were evaluated during the last week of drug infusion, while spatial memory was assessed during the 3rd month after SE. Angiotensin II decreased the latency for onset of the first SMS and increased the frequency of SMS two months after SE. The continuous peptide infusion exacerbated the KA-induced hyperactivity and caused depression-like behavior. The reduced anxiety of KA-treated rats was alleviated by Ang II exposure. The KA-induced deficit in the hippocampal-dependent spatial memory was not influenced by Ang II. However, Ang II partially prevented the neuronal damage in the hippocampus, specifically in the CA1 area. The role of AT1 and AT2 receptor activation in the effects of the octapeptide is discussed.
Subject(s)
Angiotensin II/pharmacology , Anticonvulsants/pharmacology , Behavior, Animal/drug effects , CA1 Region, Hippocampal/drug effects , Circadian Rhythm/drug effects , Kainic Acid/pharmacology , Neuroprotective Agents/pharmacology , Spatial Memory/drug effects , Status Epilepticus/drug therapy , Angiotensin II/administration & dosage , Animals , Anticonvulsants/administration & dosage , CA1 Region, Hippocampal/pathology , Disease Models, Animal , Infusions, Intraventricular , Kainic Acid/toxicity , Male , Neuroprotective Agents/administration & dosage , Rats , Rats, Wistar , Status Epilepticus/chemically inducedABSTRACT
UNLABELLED: The renin-angiotensin system plays a crucial role in the regulation of cardiovascular function and maintenance of water-electrolyte balance. The two major receptor types of the system, AT1 and AT2, have different, often opposite effects on these functions. AIM: To elucidate the impact of long-term treatment with selective angiotensin receptor antagonists and an agonist on water-salt balance in normotensive Wistar and spontaneously hypertensive rats (SHRs). MATERIALS AND METHODS: 12-week-old male Wistar rats and SHRs were individually housed in metabolic cages and 24-h food and water intake and urine and electrolyte excretion were measured. Urinary sodium (UNa), potassium (UK) and chlorine (UCl) were determined by a flame photometer. Losartan, a selective AT1 receptor antagonist, was administered in the Wistar rats and SHRs at a dose of 10 mg/kg/day subcutaneously (sc). Wistar rats were also given the AT2 receptor antagonist, PD123319, subcutaneously at a dose of 10 mg/kg/ day. CGP 42112A, an AT2 receptor agonist, was administered intracerebroventricularly in Wistar rats at a dose of 12 microg/rat/day. The drugs were infused continuously for 14 days through osmotic minipumps. RESULTS: Losartan selectively increased sodium excretion in both rat strains and decreased weight gain in SHRs. PD123319 increased potassium excretion and decreased weight gain in Wistar rats. CGP 42112A increased food and water intake, urine output and UNa+ and UK+ excretion and decreased weight gain in normotensive Wistar rats. CONCLUSIONS: Chronic treatment with selective angiotensin receptor ligands modifies water-salt balance in rats through changes both in renal excretory function and ingestive behaviors.
Subject(s)
Angiotensin Receptor Antagonists/pharmacology , Receptors, Angiotensin/agonists , Water-Electrolyte Balance/drug effects , Animals , Body Weight/drug effects , Drinking/drug effects , Eating/drug effects , Male , Oligopeptides/pharmacology , Rats , Rats, Inbred SHR , Rats, WistarABSTRACT
UNLABELLED: Accumulated evidence has shown that renin-angiotensin system has a pivotal role in stress responses. AIM: to assess the participation of AT1 receptor in stress-induced modulation of motor activity, nociception and seizure susceptibility in male Wistar rats. MATERIAL AND METHODS: AT1 receptor antagonist losartan was administered subcutaneously to rats for 10 days at a dose of 10 mg/kg either alone or as a pretreatment before chronic restraint stress applied for 10 days. Locomotor and exploratory activity (open field test), the nociception (paw-pressure test) and the seizure susceptibility (pentylenetetrazol seizure test) were analysed. RESULTS: Chronic restraint stress decreased motor activity and increased anxiety-like behaviour (grooming) while losartan pretreatment alleviated anxiety-like behaviour. Chronic restraint stress had an antinociceptive effect in paw-pressure test and losartan pretreatment abolished stress-induced antinociception. Both chronic restraint stress and losartan showed anticonvulsant activity in pentylenetetrazol seizure test. However, drug pretreatment attenuated this effect in chronically-stressed rats. CONCLUSIONS: Our findings suggest that the AT1 receptor is involved in the mechanism of stress-induced changes in anxiety-like behaviour, nociception and seizure susceptibility in rats.
