Effects of acute intravenous infusion of apelin on left ventricular function in dogs with advanced heart failure.

BACKGROUND: Apelin-13 (APLN) through apelin receptor (APJ) exerts peripheral vasodilatory and potent positive inotropic effects. We examined the effects of exogenous intravenous infusion of APLN on left ventricular (LV) systolic function in dogs with heart failure (HF, LV ejection fraction, EF~30%). METHODS AND RESULTS: Studies were performed in 7 dogs with microembolization-induced HF. Each dog received an intravenous infusion of low dose and high dose APLN followed by washout period. LV end-diastolic volume (EDV), end-systolic volume (ESV) and LV EF were measured at specified time points. APLN protein level was determined in plasma at all time points. mRNA and protein levels of APLN and APJ in LV tissue were also measured in 7 normal (NL) and 7 heart failure (HF) dogs. APLN reduced EDV only at the high dose, significantly reduced ESV and increased EF with both doses. In plasma of HF dogs, APLN levels were reduced significantly compared to NL dogs. APLN treatment in HF dogs significantly increased the plasma APLN levels at both low and high doses. Expression of APLN, but not of APJ, was reduced in LV tissue of HF dogs compared to NL. CONCLUSIONS: Exogenous administration of APLN improved LV systolic function in dogs with advanced HF.

The toxic effects of toluene on the optokinetic nystagmus in pigmented rats.

The effects of 375 mgm(-3) (100 ppm) toluene in air inhalation were evaluated on pigmented rats during either repeated exposures over five consecutive days 3h a day or during a single 4-h exposure. At the end of the inhalation period, the animals were returned to fresh air to evaluate their ability to recover optokinetic performance. The optokinetic responses were analyzed using a magnetic search coil technique previously described. After repeated toluene exposure, the eye position at rest of all the rats was unsteady. In response to visual stimulation, the eye velocity was slower and more irregular than in the control state. At the end of the stimulation, the environment of the animals became stationary, but the eye did not immediately return to a fixed stable position. A similar effect was observed after a single exposure. An increase of the optokinetic deficit was observed after single or repeated 375 mgm(-3) toluene exposures. No recovery was observed even after a single exposure. In view of the fact that toluene is a widely used solvent, these results show that inhalation of low concentrations, even for short single exposures, must be taken into account, because gaze destabilization could cause vertigo symptoms.

Effects of differential blockade of the renin-angiotensin system in postinfarcted rats.

The present study compared short-term effects of the AT(1)-receptor antagonist, irbesartan with the angiotensin-converting enzyme (ACE) inhibitor, enalapril on systemic haemodynamics and cardiac remodelling in post-myocardia-infarcted (MI) rats. MI Sprague-Dawley rats were orally treated for 4 weeks with irbesartan (50 mg/kg/day) or enalapril (10 mg/kg/day). Then, cardiac and systemic haemodynamics were measured. Compared with the sham-operated group, left ventricular end-diastolic pressure (LVEDP), diastolic pressure (LVDP), heart weight to body weight ratio were all significantly increased in the MI group while the LV contractility (dP/dt) and pulsatile arterial pressure were significantly reduced. Both drugs reduced the elevated LVEDP and LVDP and prevented cardiac hypertrophy. Furthermore, irbesartan attenuated the right shift of the pressure-volume curves, prevented postinfarction-induced increase in urinary cyclic guanosine monophosphate and reduced urinary aldosterone excretion. Although both drugs were able to prevent further cardiac hypertrophy and improved cardiac filling pressure, only irbesartan limited LV dilatation. These data indicate that blockade of the renin-angiotensin system at the level of AT1 receptors may have a better cardioprotective benefit than reducing angiotensin II levels by ACE inhibition.