Inhibition of nitric oxide‐GABA pathway by reactive oxygen species in the rostral ventrolateral medulla causes sympathoexcitation in SHRSP

Background In the rostral ventrolateral medulla (RVLM) of hypertensive rats, increased reactive oxygen species (ROS) such as superoxide (O 2 − ) increase sympathetic nerve activity (SNA), whereas nitric oxide (NO) inhibits SNA via GABA release. O 2 − interacts with NO to rapidly decrease the bioavailability of NO in vitro. We investigated whether the ROS‐induced increase in SNA is mediated by decreased GABA release through a decrease in the bioavailability of NO due to ROS in the RVLM of stroke‐prone spontaneously hypertensive rats (SHRSP). Methods and Results In SHRSP, microinfusion of an O 2 − scavenger (tempol, 10 nmol) into the RVLM decreased mean arterial pressure (MAP), heart rate (HR), and renal SNA (RSNA) and increased GABA release. Prior microinfusion of an NO synthase inhibitor (N G ‐monomethyl‐L‐arginine, L‐NMMA, 100 nmol) into the RVLM attenuated the tempol‐induced decreases in MAP, HR, and RSNA, as well as the increased GABA release (ΔMAP; −6.2±0.7% vs. −11±1.3%, ΔHR; −3.0±0.4% vs. −5.1±0.5%, ΔRSNA; −8.2±1.2% vs. −15±1.0%, ΔGABA; 23±3.2% vs. 58±12%, n=5 for each, P<0.05). Microinjection of the GABA‐A receptor antagonist bicuculline (200 pmol) into the RVLM before microinjection of tempol or L‐NMMA attenuated the tempol or L‐NMMA‐induced changes in MAP, HR, and RSNA. Conclusion Inhibition of the NO‐GABA pathway by ROS in the RVLM causes sympathoexcitation in SHRSP.