Microglial‐neuronal interactions in the paraventricular nucleus (PVN): a potential mechanism underlying neurogenic hypertension

Abstract

Neuroinflammation has been suggested to contribute to neurogenic hypertension. Microglia, the resident immune cells in the CNS, are the major source of proinflammatory cytokines (PIC). We and others have shown microglial activation and elevated activity of the renin‐angiotensin system (RAS) in the hypothalamic PVN in hypertension. Therefore we hypothesized that RAS components (prorenin and angiotensin [Ang] II) activate microglia, and that microglial activation increases PVN neuronal firing. We found that Ang II and prorenin significantly increased the expression of PIC mRNA in microglia cultured from rat hypothalamus. These increases were respectively abolished by corresponding receptor blockers. Next, we activated microglia with LPS, and tested the effect on sympathetic PVN neuronal firing. Whole cell patch‐clamp recordings were made on identified PVN neurons projecting to the vasomotor neurons in the brain stem. LPS caused a significant increase in neuronal firing frequency. These increases were abolished by minocycline, an inhibitor of microglial activation. Moreover, LPS significantly increased PIC mRNA expression in microglia. PIC receptors were highly expressed on the PVN neurons. In summary we show that RAS components activate microglia, causing increased production of PIC, which leads to the increased firing frequency of PVN neurons. AHA11SDG6770006 to PS; HL098276 to JLG; HL076803 to CS.