Liisa Näveri

Angiotensin AT2 receptor stimulation increases survival in gerbils with abrupt unilateral carotid ligation.

Previous studies showed that angiotensin II (AII) infusion increased survival in gerbils subjected to abrupt unilateral carotid ligation. Recently, stimulation of the AII AT2 receptor, reportedly effectively extended the blood pressure (BP) range of cerebral blood flow (CBF) autoregulation. We evaluated the survival of gerbils treated with PD-123319, a ligand of AT2 receptors, to test the hypothesis that restoration of BF to ischemic cerebral tissue produced by AII is mediated through AT2 receptors. Abrupt unilateral carotid ligation was performed on 300 gerbils. In five experimental groups, animals received no drug pretreatment: (a) saline; (b)-(d) PD-123319 1.0, 3.0, and 10 mg/kg; and (e) losartan 10 mg/kg. In three additional experimental groups, animals were pretreated with enalaprilat: (f) saline; (g) PD-123319, 10 mg/kg, and (h) losartan, 10 mg/kg. Survival for 48 h was significantly improved by PD-123319 (10 mg/kg) (p < 0.05) and by losartan (10 mg/kg) (p < 0.05) as compared with animals injected with saline. Pretreatment with enalaprilat neutralized the protective effect of losartan. PD-123319 is an AT2 agonist and improved survival in this animal model of stroke. Losartan, an AT1 antagonist, also improved survival, possibly through renin release and AT2 stimulation by endogenous AII. This effect was neutralized by enalaprilat.

Angiotensin AT2 receptors regulate cerebral blood flow in rats

Large cerebral arteries have been reported to contain angiotensin receptors that are exclusively of the AT2 subtype. We measured the effect of the AT2 receptor selective ligand PD 123319 on cerebral blood flow (CBF) in rats, using laser-doppler flowmetry. PD 123319 (1–10 mg kg-1) dose-dependently inhibited the increase in CBF, when the blood pressure was increased by a norepinephrine infusion. However, PD 123319 did not alter baseline CBF at normal blood pressures. Therefore PD 123319 appears to interfere with the autoregulatory mechanisms of CBF. The participation of AT2 receptors in the regulation of CBF confirms a physiological role for this receptor subtype, and may give clues for future treatment of various cerebrovascular disorders.

Angiotensin II AT1 receptor mediated contraction of the perfused rat cerebral artery.

The effect of angiotensin II on rat cerebral arteries was studied using isolated, perfused segments of anterior cerebral arteries. The infusion rate was set to maintain baseline intraluminal pressure at 75 mmHg. Angiotensin II (100 nM) increased the intraluminal pressure by 22.5 +/- 2.2 mmHg. Losartan, an AT1 antagonist, at 1 microM, completely blocked the effect of angiotensin II, whereas the AT2 ligands PD 123319 (1 microM) and CGP 42112 (1 microM) were ineffective. None of these AT1 or AT2 selective ligands alone displayed any agonist effects. The results show that angiotensin II induces contraction of the rat anterior cerebral artery by acting on AT1 receptors.

Effects of Ceronapril Alone or in Combination with Alcohol on Psychomotor Performance in Healthy Volunteers: A Placebo-Controlled, Crossover Study

Abstract Background: Behavioral evidence from animal studies has suggested that ceronapril and other angiotensin-converting enzyme (ACE) inhibitors have some anxiolytic activity. Objectives: The objectives of this trial were to assess the effects of ceronapril, a centrally acting ACE inhibitor, on psychomotor performance in healthy volunteers; to compare its effects with those of lorazepam, a known anxiolytic agent; and to determine whether ceronapril interacts pharmacodynamically with alcohol. Methods: Twelve healthy male volunteers received ceronapril (80 mg), lorazepam (2 mg), or corresponding placebo twice daily for 7 days in a randomized, double-blind, placebo-controlled, crossover study. Psychomotor tests were performed on days 1 and 7 of each treatment period. On the testing days, the subjects ingested alcohol (1 g/kg) over a 30-minute period, 2 hours after drug administration. Psychomotor tests (simulated driving task, critical flicker fusion, body sway, lateral-gaze nystagmus, Maddox wing test, Mini—Mental State Examination, and subjective assessments) were performed before the administration of the morning dose and 1 hour, 3 hours (40 minutes post-alcohol), and 4 hours (100 minutes post-alcohol) after drug administration. Results: On day 1, ceronapril did not impair psychomotor performance, and its effects were comparable to those of placebo before and after alcohol ingestion. Lorazepam impaired most of the psychomotor functions, and its effects were enhanced by alcohol. On day 7, ceronapril decreased systolic blood pressure, but otherwise its effects were similar to those of placebo. Due to development of tolerance, lorazepam had few psychomotor effects after the subchronic administration. Conclusions: Ceronapril was found to have no anxiolytic effects or effects on psychomotor performance in this sample of healthy volunteers.

Angiotensin Receptor Subtypes and Cerebral Blood Flow

The brain receives approximately 15% of the cardiac output to maintain a blood flow rate of around 50 ml/100 g tissue per min. The cerebral circulation is secured by two separate vascular channels: the carotid arteries and the vertebrobasilar system These systems meet at the base of the brain in a vascular ring known as the circle of Willis.1 Due to this complex anatomy, cerebral blood flow (CBF) can be maintained even if one of the vascular territories fails. The cerebral arteries are innervated by sympathetic, parasympathetic, and sensory nerve fibers, each type containing several potential neurotransmitters.1 Furthermore CBF is controlled by local metabolic, or chemical, factors.1

Teachers’ Activities During a Mathematics Lesson as Seen in Third Graders’ Drawings

Third-graders from 19 classrooms (N = 316) were asked to draw a picture on a mathematics lesson. Based on these drawings we have produced a list which can be used to analyze how young pupils describe in their drawings their teacher’s activities during mathematics lessons. This list contains items: Teacher is giving information on mathematics, Teacher is giving instructions, Teacher is asking questions, Teacher is giving feedback, and Teacher is reflecting. In addition, the list contains information on whether the pupils have drawn the teacher at all, whether the teacher is quiet or talking, and what the teacher’s location is in the classroom. In order to show the functioning of the list we give some results of the analysis.

Developing a method to determine teachers’ and pupils’ activities during a mathematics lesson

Third-graders from nineteen classrooms (N = 316) were asked to draw a picture on a mathematics lesson. Based on these drawings we have developed a data analysing method that allows us to find out how pupils present both their teacher’s and their classmates’ activities in their drawings. Two inventories were formed that contain, respectively, teachers’ and pupils’ activities during a mathematics lesson as seen in the pupils’ drawings. The first inventory contains 14 separate items organized into six groups that contain teacher activities like asking questions and giving feedback on mathematics. Ten of the items are related to teaching and the rest contain items like keeping order in addition to the teacher’s location in the classroom. Respectively, pupils’ activities are organized into five groups that contain altogether 22 items. These contain the activities of a single pupil, and also pupil-teacher and pupil-pupil discussions on mathematics.