Key result
IV LY379268 reduces MAP by ~14 mmHg vs saline in hypertensive rats.
Why the study?
Intracisternal mGluR2/3 agonists attenuate hypertension but have limited clinical applicability, prompting investigation into whether systemic administration of LY379268 modulates central blood pressure regulation.
Does intravenous administration of the selective mGluR2/3 agonist LY379268 reduce arterial blood pressure in spontaneously hypertensive rats?
Does intravenous administration of the selective mGluR2/3 agonist LY379268 reduce arterial blood pressure in spontaneously hypertensive rats?
Answers are grounded in this paper and cite their sources.
Systemic intravenous administration of the mGluR2/3 agonist LY379268 attenuates hypertension in spontaneously hypertensive rats, suggesting a potential minimally invasive strategy for targeting central mechanisms of hypertension.
Hypertension is associated with impaired central autonomic regulation and remains a major risk factor for cardiovascular diseases. The nucleus tractus solitarius (NTS) in the medulla oblongata plays a critical role in blood pressure control via glutamatergic neurotransmission from peripheral baroreceptors. Previous studies have shown that intracisternal administration of Group II metabotropic glutamate receptor (mGluR2/3) agonists attenuates hypertension; however, the clinical applicability of this invasive approach is limited. The present study investigated whether systemic administration of a selective mGluR2/3 agonist, LY379268, can modulate central blood pressure regulation and attenuate hypertension. LY379268 was administered intravenously to spontaneously hypertensive rats (SHRs). In anesthetized conditions, arterial blood pressure and heart rate were continuously recorded and dose–response effects were evaluated. In conscious conditions, LY379268 were administered into the tail vein of control SHRs or SHRs with intact (Sham) or preoperatively transected baroreceptor information (Sino-aortic denervation, SAD), and blood pressure was periodically measured by the tail-cuff method. A dose-dependent reduction in arterial blood pressure without significant changes in heart rate was observed up to moderate doses (10 μg/kg), showing bell-shape response. Similarly, aforementioned dose of LY379268 i.v. injection decreased blood pressure in control or Sham-SHRs but not in SAD-SHRs in conscious condition. In addition, intravenous Evans blue injection demonstrated increased permeability of the blood-brain-barrier in the NTS. These findings indicate that systemic activation of mGluR2/3 can attenuate hypertension by modulating central autonomic regulation via access to the NTS. Intravenous administration of mGluR2/3 agonists may represent a minimally invasive strategy for targeting central mechanisms underlying hypertension.
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Aoki et al. (2026) studied hypertension. LY379268 vs. Saline was evaluated on Mean arterial blood pressure changes after intravenous administration (null, 95% CI null, p=0.002). LY379268 administered intravenously reduced mean arterial blood pressure by 13.7 mmHg compared to saline in conscious spontaneously hypertensive rats at 45 minutes post-administration.
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