Ang-(1–7) activates the NO/cGMP and ATP-sensitive K+ channels pathway to induce peripheral antinociception in rats

Angiotensin-(1–7) through Mas receptor activation induces peripheral antinociception by interaction with adrenoreceptors

“…This modulation appear be dependent of its interaction with Mas receptor [11]. Until now, it had been suggested that not opioid, but activation of NO/cGMP pathway was involved in the mechanism by which Ang-(1-7) induce peripheral antinociception [11,12]. In the present study, peripheral antinociception by Ang-(1-7) was dependent of its interaction with adrenergic system.…”

“…Although, Ang-(1-7) was able to induce an increase in nitrite levels, activating nNOS (neuronal nitric oxide synthase) at peripheral sites inducing antinociception through NO release. NO in turn activated cGMP causing the opening of K+ channels in the peripheral sensitive neuron and thus analgesia [12].…”

Angiotensin-(1-7)/Mas receptor as an antinociceptive agent in cancer-induced bone pain

“…8 We administered Ang-(1-7) systemically (0.360, 1, 10 μg/kg, i.p.) in naive mice and observed a small but significant increase in thermal tail flick latencies.…”

“…41 Phosphorylation of spinal p38 MAPK has been observed in chronic injury, 77 and therefore a decrease in phospho-p38 MAPK in chronic injury models such as CIBP may prove to yield antinociceptive effect. MasR activation by Ang-(1-7) can activate nitric oxide synthase, increasing intracellular NO 8 to further increase intracellular levels of cyclic GMP (cGMP). cGMP production leads to the activation of ATP-dependent potassium channels, thereby hyperpolarizing the neuron, 1,2,50 in addition to blocking voltage-gated calcium channels that will slow or block neurotransmitter release.…”

Fosinopril Prevents the Development of Tactile Allodynia in a Streptozotocin‐Induced Diabetic Rat Model

“…Inhibition of angiotensin II synthesis leads to accumulation of angiotensin I [Lawrence et al, 1992;Luque et al, 1996;Yamada et al, 1998], which in turn is converted to angiotensin1-7, by ACE 2, that then activates the Mas receptor leading to antinociception [Yang et al, 2011;Costa et al, 2012;Xing et al, 2012;Pacheco et al, 2013;Nemoto et al, 2014]. Reports suggest that angiotensin1-7 produces antinociception by activation of the L-arginine-nitric oxide-cyclic GMP-ATP-sensitive K 1 channels pathway [Yang et al, 2011;Costa et al, 2014]. The antinociceptive effect of fosinopril was accompanied with partial reduction in weight loss and hyperglycemia as well as a small reduction in systolic blood pressure but not in heart rate nor insulin levels in diabetic rats.…”