Heart rate reduction after genetic ablation of L-type Ca1.3 channels induces cardioprotection against ischemia-reperfusion injury.

Background: Acute myocardial infarction (AMI) is the major cause of cardiovascular mortality worldwide. Most ischemic episodes are triggered by an increase in heart rate, which induces an imbalance between myocardial oxygen delivery and consumption. Developing drugs that selectively reduce heart rate by inhibiting ion channels involved in heart rate control could provide more clinical benefits.

Inertial Measurement of Head Tilt in Rodents: Principles and Applications to Vestibular Research.

Inertial sensors are increasingly used in rodent research, in particular for estimating head orientation relative to gravity, or head tilt. Despite this growing interest, the accuracy of tilt estimates computed from rodent head inertial data has never been assessed. Using readily available inertial measurement units mounted onto the head of freely moving rats, we benchmarked a set of tilt estimation methods against concurrent 3D optical motion capture.

Effect of the novel histamine H receptor antagonist SENS-111 on spontaneous nystagmus in a rat model of acute unilateral vestibular loss.

Background And Purpose: Histamine H receptors are expressed in the peripheral vestibular system, and their selective inhibition improves vertigo symptoms in rats with unilateral vestibular lesions. The effects of SENS-111, a selective oral H receptor antagonist with high affinity to both animal and human receptors, on vertigo symptoms was evaluated in a translational in vivo model of unilateral vestibular loss.

Experimental Approach: Pharmacokinetics of SENS-111 in rats was determined to aid dose selection for efficacy testing.

Cardiac mGluR1 metabotropic receptors in cardioprotection.

Aims: In a previous study using a genome-wide microarray strategy, we identified metabotropic glutamate receptor 1 (mGluR1) as a putative cardioprotective candidate in ischaemic postconditioning (PostC). In the present study, we investigated the role of cardiac mGluR1 receptors during cardioprotection against myocardial ischaemia-reperfusion injury in the mouse myocardium.

Methods And Results: mGluR1 activation by glutamate administered 5 min before reperfusion in C57Bl/6 mice subjected to a myocardial ischaemia protocol strongly decreased both infarct size and DNA fragmentation measured at 24 h reperfusion.

Counteracting neuronal nitric oxide synthase proteasomal degradation improves glucose transport in insulin-resistant skeletal muscle from Zucker fa/fa rats.

Aims/hypothesis: Insulin-mediated glucose transport and utilisation are decreased in skeletal muscle from type 2 diabetic and glucose-intolerant individuals because of alterations in insulin receptor signalling, GLUT4 translocation to the plasma membrane and microvascular blood flow. Catalytic activity of the muscle-specific isoform of neuronal nitric oxide synthase (nNOS) also participates in the regulation of glucose transport and appears to be decreased in a relevant animal model of drastic insulin resistance, the obese Zucker fa/fa rat. Our objective was to determine the molecular mechanisms involved in this defect.