4 research outputs found
The angiotensin-(1-7)/Mas receptor axis is expressed in sinoatrial node cells of rats.
The authors’ previous studies have indicated that angiotensin(Ang)-(1-7) protects the heart against reperfusion arrhythmias.
The aim of this study was to determine whether a functional angiotensin-converting enzyme2 (ACE2)/Ang-(1-7)/Mas receptor
axis is present in the sinoatrial node (SAN) of Wistar rats. SAN cells were identified by Masson’s trichrome staining, HCN4
expression, and lack of connexin43 expression. Immunohistochemistry technique was used to detect the expression of ACE2,
Ang-(1-7), and Mas in the SAN. To evaluate the role of this axis in the SAN function, atrial tachyarrhythmias (ATs) were induced
in isolated rat atria perfused with Krebs-Ringer solution (KRS) alone (control) or KRS containing Ang-(1-7). The specific Mas
antagonist, A-779, was used to evaluate the role of Mas in the Ang-(1-7) effects. The findings showed that all components of
the ACE2/Ang-(1-7)/Mas branch are present in the SAN of rats. Importantly, it was found that this axis is functional because
perfusion of atria with Ang-(1-7) significantly reduced the duration of ATs. Additionally, this anti-arrhythmogenic effect was
attenuated by A-779. No significant changes were observed in heart rate, contractile tension, or ±dT/dt. These observations
demonstrate that the ACE2/Ang-(1-7)/Mas axis is expressed in SAN cells of rats. They provide the morphological support to
the anti-arrhythmogenic effect of Ang-(1-7). (J Histochem Cytochem 59:761–768, 2011)
Antiarrhythmogenic effects of a neurotoxin from the spider Phoneutria nigriventer.
In this study, we evaluated the effects of PhKv, a 4584 Da peptide isolated from the spider
Phoneutria nigriventer venom, in the isolated rat heart and in isolated ventricular myocytes.
Ventricular arrhythmias were induced by occlusion of the left anterior descending coronary
artery for 15 min followed by 30 min of reperfusion. Administration of native PhKv
(240 nM) 1 min before or after reperfusion markedly reduced the duration of arrhythmias.
This effect was blocked by atropine, thereby indicating the participation of muscarinic
receptors in the antiarrhythmogenic effect of PhKv. Notably, recombinant PhKv (240 nM)
was also efficient to attenuate the arrhythmias (3.8 0.9 vs. 8.0 1.2 arbitrary units in
control group). Furthermore, PhKv induced a significant reduction in heart rate. This
bradycardia was partially blunted by atropine and potentiated by pyridostigmine. To
further evaluate the participation of acetylcholine on the PhKv effects, we examined the
release of this neurotransmitter from neuromuscular junctions. It was found that Phkv
(200 nM) significantly increased the release of acetylcholine in this preparation. Moreover,
PhKv (250 nM) did not cause any significant change in action potential or Ca2Ăľ transient
parameters in isolated cardiomyocytes. Altogether, these findings show an important
acetylcholine-mediated antiarrhythmogenic effect of the spider PhKv toxin in isolated
hearts