Combined Electroacupuncture Attenuates Inflammation and Hypertension in Salt-Sensitive Rats Through α-7 Nicotinic Acetylcholine Receptors

Introduction: Key hallmarks of hypertension include inflammation. Low-grade chronic inflammation is detected in hypertensive (HTNive) patients and rodent models including the dahl salt-sensitive hypertensive (DSSH) rats. We have shown that combined electroacupuncture (cEA) stimulating both the deep peroneal and the tibial nerves simultaneously at two sets of acupoints ST36-37 and SP6-7 decreased blood pressure (BP) and proinflammatory cytokines in HTNive rats through sympathoinhibition and anti-inflammation. Acetylcholine (ACh), the primary neurotransmitter of parasympathetic nerves, participates in modulation of inflammation. We hypothesized that α-7 nicotinic acetylcholine receptor (α7nAChR) contributes to the anti-inflammatory action of EA in lowering BP in DSSH rats. Methods: 20 DSS rats were randomly allocated into five groups (4 rats/group). Four groups were fed with 4% salt diet to develop hypertension; one group was fed with normal diet and served as normotensive (NTNive) controls. Once moderate hypertension (SBP 160±5 mmHg) was established, the four HTNive groups were randomized to receive five weeks of cEA or Sham-EA (no electrical stimulation), or daily intraperitoneal (ip) of PNU-282987 (4.8 mg/kg), a selective α7nAChR agonist, or vehicle (2% DMSO in peanut oil). In a similar manner, another 16 DSS rats were allocated into three HTNive groups and one NTNive group. The HTNive groups were treated with Sham-EA, or cEA + saline, or cEA + methyllycaconitine (MLA), a α7nAChR antagonist. Both cEA and Sham-EA were given twice weekly for eight weeks. MLA (2.4 mg/kg) or saline vehicle was administrated daily via ip during the last three weeks of cEA or Sham-EA treatments. Systolic/diastolic BP (SBP/DBP) were measured with Tail-cuff via CODA system once a week. Results: At the end of the experiment, five weeks of cEA decreased SBP by 22.1±4.4 mmHg and decreased DBP by 26.8±16.7 mmHg compared to pre-cEA conditions (SBP: 162±1.8 mmHg, DBP: 110±12.2 mmHg). In contrast, five weeks of PNU-282987 did not decrease BPs but prevented BPs from continual increase. Compared to Sham-EA treated rats (SBP: 187±3.5 mmHg, DBP: 141±6.2 mmHg), five weeks of cEA decreased SBP by 25.5% to 140±7.1 mmHg and DBP by 32.5% to 95±15.1 mmHg; five weeks of PNU-282987 decreased SBP by 14.6% to 160±5.0 mmHg and DBP by 20.6% to 112±3.0 mmHg. Three additional weeks of α7nAChR blockade with MLA partially reversed the cEA induced BP reduction to severe HTNive ranges (SBP: 193±5.2 mmHg, DBP: 137±4.8 mmHg), while the reversed BPs in cEA+MLA treated rats were still significantly lower than Sham-EA-treated rats (SBP: 208±4.9 mmHg, DBP: 145±6.4 mmHg). BPs of NTNive rats remained in the normal BP ranges throughout the experiments. Conclusion: These data suggested that systemic agonist of α7nAChR with PNU-282987 prevented mild-to-moderate hypertension from further developing to the severe state, while α7nAChR antagonism with MLA partially reversed the BP-lowering effects of cEA in DSSH rats. Therefore, we concluded that the α7nAChR plays an important role in the effects of cEA in alleviating hypertension. This study was supported by the National Health Institute funding NIH 1RO1AT011306-01A1. This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.