Increased Excitability of Renal Sensory Neurons by Vasopressin in Male and Female Sprague Dawley Rats.

BACKGROUND: Preclinical models of cardiovascular and kidney diseases, such as hypertension and polycystic kidney disease (PKD), are associated with increased vasopressin (AVP) and increased renal afferent nerve activity (ARNA). We have also shown that ablation of renal sensory nerves can mitigate HTN and PKD progression in preclinical models. Yet, the underlying cause of elevated renal sensory nerve activity in disease remains unclear, and the role of vasopressin remains untested. Therefore, we hypothesized that AVP would increase the excitability of renal-specific dorsal root ganglia neurons (rDRGN) in both male and female rats.

METHODS: To address this hypothesis, rDRGN were isolated from both male and female Sprague-Dawley (SD) rats and cell excitability changes with AVP were measured by whole-cell patch clamp in current-clamp mode. Excitability was quantified by mean action potential (AP) frequency, rheobase, and multi-firing threshold. Dose-dependent responses to AVP (10-12-10-6M) were measured and compared to vehicle (saline).

RESULTS: Cell excitability was increased by AVP in both male and female cells, increasing AP frequency and lowering rheobase and multi-firing threshold. The effective excitatory range of AVP was 10-10-10-6M in female cells, and 10-8-10-6M in males.

CONCLUSIONS: These experiments support our initial hypothesis that AVP would directly increase rDRGN excitability. This excitatory effect may support a novel role through which peripheral sensory nerves interact with and respond to AVP. In turn, this AVP-ARNA interaction may contribute to elevated peripheral sensory nerve activity and disease progression where AVP is elevated, such as hypertension and PKD.