RESUMO
Endorphins are endogenous opioid neuropeptides that are mainly produced from pituitary gland in response to pain and different triggers including interleukin 1 beta (IL-1ß) and corticotropin-releasing factor (CRF). Angiotensin II (Ang II) can stimulate ß-endorphin production, but the exact molecular mechanisms involved in this effect, and the role of the released ß-endorphin in Ang II-mediated pressor response remain elusive. Male rats were injected with IL-1ß receptor antagonist (IL-1Ra, 100 µg/kg), the CRF receptor blocker, astressin (20 µg/rat) or a combination of both, prior to Ang II injection (200 µg/kg). Another group of rats was given naloxone (1.6 mg/kg) or telmisartan (5 mg/kg) before Ang II injection. Blood pressure and serum and Paraventricular nucleus (PVN) ß-endorphin were detected. Moreover, IL-1ß and CRF as well as markers of oxidative stress [malondialdehyde (MDA) and superoxide dismutase (SOD)], inflammation [C-reactive protein (CRP)] and neuronal activation (c-Fos, l-glutamate, and phosphorylated ERK) were measured in the PVN of different groups. Ang II induced a pressor response and increased serum and PVN ß-endorphin levels that were attenuated in rats pre-treated with astressin or/and IL-1Ra. Moreover, Ang II increased PVN oxidative stress, inflammation and neuronal activation. Telmisartan abolished the previous effects, while naloxone, astressin and IL-1Ra aggravated Ang II-mediated pressor response and most of the biochemical changes. These findings suggest that, Ang II can induce ß-endorphin release via increasing both IL-1ß and CRF levels which in result mitigates Ang II-mediated central responses. This study highlights ß-endorphin as a possible target for treating hypertension.
