Exogenous nicotinamide adenine dinucleotide (NAD+): effects and mechanisms of action on the mammalian heartстатьяТезисы
Статья опубликована в высокорейтинговом журнале
Информация о цитировании статьи получена из
Web of Science
Статья опубликована в журнале из списка Web of Science и/или Scopus
Дата последнего поиска статьи во внешних источниках: 9 марта 2017 г.
Аннотация:OBJECTIVES. Nicotinamide adenine dinucleotide (NAD+) is well known compound, playing central role in cellular metabolism and energy turnover. Recently, NAD+ has been regarded as potential neurotransmitter, since releasing from nerve endings was demonstrated. Effects of extracellular NAD+ as regulatory compound is not completely investigated, especially in the hearts. This study is aimed to the investigation of the NAD+ effects and mechanisms of action in a mammalians heart.
METHODS. Multicellular preparations of left atria (LA), right atria (RA), sinoatrial node (SAN), right ventricular wall (RV) were dissected from male Wistar (200-250 g) rats hearts and perfused in standard conditions with Tirode solution. Also, multicellular preparations of rabbit Purkinje fibers (PF) were used in experiments. Action potentials (APs) were recorded with use of standard microelectrode technique under control conditions and after NAD+, ATP or adenosine administration (1-100 mcM). APs duration at level of 90% repolarization (APD) were estimated. APs were recorded in electrically paced (LA, RA, RV, PF, SS=300 ms) or spontaneously active preparations (SAN).
RESULTS. NAD+ (10 and 100 mcM) induces significant (p(T)<0.05) decreasing of APD in rat LA (to 77±3% and 65±2 % in respect to control APD, n=8), RA (78±4% and 66±3%, n=5) and RV (57±6% and 70±5%, n=6).
Also, NAD+ induces shortening of APs in PF (91±3%, 100 mcM, p(T)<0.05, n=5). Administration of NAD+ caused decreasing of rate of spontaneous firing, slow diastolic depolarization and APD in rat SAN.
APDs decreasing after 1-100 mcM NAD+ administration were similar to those, induced by ATP or adenosine (1-100 mcM). NAD+- induced APs alternation, in contrast with adenosine, was not suppressed by P1-purinoreceptor antagonist theophylline (100 mcM, n=8). P2 antagonist suramine (10 mcM, n=10) completely attenuated APs shortening caused by 10-100 mcM NAD+ in rat preparations (p(U)<0.05).
CONCLUTIONS. Exogenous NAD+ have significant influence on the bioelectrical activity of pacemaker, atrial and ventricular myocardium. Metabolite independent, direct NAD+ action via P2-purinoreceptros is suggested.