Endogenous β‐endorphin Plays a Pivotal Role in Angiotensin II‐mediated Pressor Response

Abstract

BackgroundEndorphins are endogenous opioid neuropeptides that are mainly produced from the pituitary gland in response to pain and stress. A number of mediators were reported to stimulate β‐endorphin production including interleukin 1 beta (IL‐1β) and corticotropin‐releasing factor (CRF). Angiotensin II (Ang II) can stimulate β‐endorphin production from anterior pituitary gland, but the exact molecular mechanisms involved in this effect, as well as the role of the released β‐endorphin in Ang II‐mediated pressor response, remain elusive. Our study aimed to fill this knowledge gap.MethodsMale rats (6 per group) were either injected with IL‐1β receptor blocker (IL‐1R antagonist, 100 μg /kg, s.c.), the CRF receptor blocker, astressin (100 μg /kg, Intranasal) or a combination of both prior to Ang II injection (200 μg/kg, ip). Other groups of rats were given naloxone (1.6 mg/kg, s.c.) or telmisartan (10 mg/kg, oral) prior to Ang II injection. Serum and hippocampal β‐endorphin levels, brain IL‐1β and CRF levels were detected. Moreover, markers of oxidative stress including malondialdehyde (MDA) and superoxide dismutase (SOD), the inflammatory marker, C‐reactive protein (CRP) and sympathoexcitation (c‐Fos, L‐glutamate, and phosphorylated MAPK) markers were measured in the hippocampus of different groups.ResultsAng II increased serum and hippocampal β‐endorphin levels by 37.95% and 28.03%, respectively. This response was attenuated when astressin or/and IL‐1R antagonist were given before Ang II injection. Moreover, Ang II induced a pressor response, increased hippocampal IL‐1β (1.4‐fold), CRF (7‐fold), MDA (1.5‐fold) and CRP (3.3‐fold) while deceased SOD (by 31.49%) levels. Also, Ang II injection increased c‐Fos (9.9‐fold), glutamate (3.1‐fold) and phosphorylated‐MAPK (5.6‐fold) levels. The previous effects were abolished when telmisartan was given prior to Ang II injection, while naloxone aggravated Ang II‐mediated pressor response and most of the biochemical changes.ConclusionThese findings suggest that Ang II can induce β‐endorphin release by increasing the levels of both IL‐1β and CRF and that the released endorphin mitigates Ang II‐mediated sympathoexcitatory response. This study reveals new insights on the intermediary role of β‐endorphin in Ang II‐mediated sympathoexcitation and highlights it as a possible target for treating hypertension.