A novel functional role for classic CNS neurotransmitters, GABA, glycine and glutamate, in the kidney: potent and opposing regulators of the renal vasculature

The presence of a renal GABA/glutamate system has previously been described; however, its functional significance in the kidney remains undefined. We hypothesized given its extensive presence in the kidney that activation of this GABA/glutamate system would elicit a vasoactive response from the renal microvessels. Functional data here demonstrate for the first time that activation of endogenous GABA and glutamate receptors in the kidney significantly alters microvessel diameter with important implications for influencing renal blood flow. Renal blood flow is regulated in both the renal cortical and medullary microcirculatory beds via diverse signaling pathways. GABA- and glutamate-mediated effects on renal capillaries are strikingly similar to those central to the regulation of CNS capillaries, that is, exposing renal tissue to physiological concentrations of GABA, glutamate and glycine led to alterations in the way contractile cells, perictyes and smooth muscle cells, regulate microvessel diameter in the kidney. Since dysregulated renal blood flow is linked to chronic renal disease, alterations in the renal GABA/glutamate system, possibly through prescription drugs, could significantly impact long-term kidney function. Key words: GABA, glutamate, Glycine, microvascular function, pericytes.

New and Noteworthy: Functional data here offers novel insight into the vasoactive activity of the renal GABA/glutamate system. This data shows that activation of endogenous GABA and glutamate receptors in the kidney significantly alters microvessel diameter. Furthermore, it shows that these antiepileptic drugs are as potentially challenging to the kidney as NSAIDs.