ABSTRACT
AIM: To investigate the effect of chronic intermittent hypobaric hypoxia (CIHH) on the activity of adrenergic receptor(AR) in rabbit sino-atrial node (SAN) by intracellular recording.METHODS: New Zealand rabbits were randomly divided into three groups: control group (Con), 14 d CIHH treatment group (CIHH14) and 28 d CIHH treatment group (CIHH28). The CIHH rabbits were exposed to a simulated 5 000 m (oxygen 11.1%) hypobaric hypoxia in hypoxic chamber for 14 d or 28 d (6 h/d), respectively. SAN preparation was used and the transmembrane action potential was recorded by micropipettes. Isoproterenol hydrochloride (ISO, agonist of β-AR) and phenylephrine (PE, agonist of α_1-AR) at different concentrations (0.01, 0.1 and 1 μmol/L) were applied cumulatively to investigate the electrophysiological effect of the drugs on the rabbit SAN among Con, CIHH14 and CIHH28 groups, respectively. RESULTS: (1) CIHH didnt change the parameters of action potential of SAN recorded under basic condition. (2) ISO changed some parameters of AP significantly in a dose-dependent manner, including increases in the amplitude of AP (APA), maximal rate of depolarization (V_(max)), the velocity of diastolic (phase 4) depolarization (VDD), and rate of pacemaker firing (RPF). (3) The response of AP to ISO in CIHH rabbits was decreased significantly compared to that in Con animals. Under 1 μmol/L of ISO, the increases in VDD, RPF, APA and V_(max) in CIHH animals were smaller than those in Con animals (P<0.05). (4) No effect of PE (0.01, 0.1 and 1 μmol/L) on the parameters of action potential was observed. CONCLUSION: CIHH decreases the reactivity of β-AR, but has no effect on α_1-AR in SAN of rabbit.
ABSTRACT
AIM To investigate the protective effect of polydatin on ischemia-reperfusion (I-R) injury in cardiac muscle and the possible mechanism. METHODS Langendorff technique was used to make I-R injury in rats. Male Sprague-Dawley rats were randomly divided into control, model, polydatin(25, 50 and 75 μmol·L-1), glibenclamide(Gli, 10 μmol·L-1)+polydatin(50 μmol·L-1), 5-hydroxydecanoate(5-HD, 100 μmol·L-1)+polydatin(50 μmol·L-1), and atractyloside (Atr, 20 μmol·L-1)+polydatin(50 μmol·L-1) groups. The hearts in control group were perfused with K-H solution for 110 min. Model group hearts were subjected to 30 min no-flow global ischemia followed by 60 min of reperfusion. The hearts in 3 polydatin groups were perfused with K-H solution containing different concentrations of polydatin for 10 min before I-R. The hearts in Gli+polydatin and 5-HD+polydatin groups were perfused with K-H solution containing Gli or 5-HD for 5 min firstly, then perfused with K-H solution containing both polydatin and Gli or 5-HD for 10 min before I-R. The hearts in Atr+polydatin group were perfused with K-H solution containing polydatin for 10 min before I-R and perfused with K-H solution containing Atr for 15 min after I-R. The cardiac function, including left ventricular end-diastolic pressure (LVEDP), left ventricular developed pressure (LVDP), the maximal rates of rise and decline of left ventricular pressure (±dp/dtmax), and coronary flow (CF), were recorded before, after 30 min no-flow global ischemia and, during 60 min reperfusion. Myocardial infarct size was assessed using 2, 3, 5-triphenyltetrazolium chloride method and myocardial ultrastructure was observed via transmission electron microscope after 60 min reperfusion. RESULTS There were no significant differences in cardiac functional parameters between control and model groups in pre-ischemia condition. Compared with model group, polydatin promoted a better recovery of cardiac function after I-R in a concentration-dependent manner. After 60 min of reperfusion, the values of LVDP, ±dp/dtmax and CF in polydatin groups were much higher, but LVEDP was lower than those in model group. Polydatin (50 μmol·L-1) also significantly reduced myocardial infarct size and relieved the I-R injury of myocardial ultrastructure. The protective effects of polydatin (50 μmol·L-1) on LVDP, LVEDP, ±dp/dtmax and CF, as well as the inhibitory effect on infarct size after I-R were abolished by Gli, 5-HD and Atr. CONCLUSION Polydatin has protective effect against I-R injury in rat hearts, which may be related with the opening of ATP-sensitive potassium channel located in both cell membrane and mitochondrial membrane, as well as inhibition of mitochondrial permeability transition pore opening.