Effect of angiotensin-(1-7) on reperfusion arrhythmias in isolated rat hearts.
There is increasing evidence that angiotensin-(1-7)(Ang-(1-7)) is an endogenous biologically active component of the renin-angiotensin system(RAS). In the present study, we investigated the effects of Ang-(1-7) on reperfusion arrhythmias in isolated rat hearts. Isolated rat hearts were perfused with two different media, i.e., Krebs-Ringer (2.52 mM CaCl2) and low-Ca2+ Krebs-Ringer (1.12 mM CaCl2). In hearts perfused with Krebs-Ringer, Ang-(1-7) produced a concentration-dependent (27-210 nM) reduction in coronary flow (25% reduction at highest concentration), while only slight and variable changes in contraction force and heart rate were observed. Under the same conditions, angiotensin II (Ang II; 27 and 70 nM) produced a significant reduction in coronary flow (39% and 48%, respectively) associated with a significant increase in force. A decrease in heart rate was also observed. In low-Ca2+ Krebs-Ringer solution, perfusion with Ang-(1-7) or Ang II at 27 nM concentration produced similar changes in coronary flow, contraction force and heart rate. In isolated hearts perfused with normal Krebs-Ringer, Ang-(1-7) produced a significant enhancement of reperfusion arrhythmias revealed by an increase in the incidence and duration of ventricular tachycardia and ventricular fibrillation (more than 30-min duration). The facilitation of reperfusion arrhythmias by Ang-(1-7) was associated with an increase in the magnitude of the decreased force usually observed during the postischemic period. The effects of Ang-(1-7) were abolished in isolated rat hearts perfused with low-Ca2+ Krebs-Ringer. The effect of Ang II (27 nM) was similar but less pronounced than that of Ang-(1-7) at the same concentration. These results indicate that the heart is a site of action for Ang-(1-7) and suggest that this heptapeptide may be involved in the mediation of the cardiac effects of the RAS.
Neves
L A
LA
Departamento de Fisiologia e Biofísica, Universidade Federal de Minas Gerais, Belo Horizonte, Brasil.
Almeida
A P
AP
Khosla
M C
MC
Campagnole-Santos
M J
MJ
Santos
R A
RA
D000804:Angiotensin II / Q000627:therapeutic use*; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000188:drug therapy*; D006339:Heart Rate / Q000187:drug effects*; D066298:In Vitro Techniques; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D015425:Myocardial Reperfusion; D009638:Norepinephrine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012084:Renin-Angiotensin System / Q000502:physiology*; D014662:Vasoconstrictor Agents / Q000627:therapeutic use*
D014662:Vasoconstrictor Agents; D000804:Angiotensin II; D009638:Norepinephrine