Superoxide scavenging in the rostral ventrolateral medulla blunts the pressor response to peripheral chemoreflex activation

Peripheral chemoreflex activation has been considered the key drive for the overactivity of the sympathetic nervous system observed in some pathological conditions such as sleep obstructive apnea. In addition, increases in angiotensin-II-derived reactive oxygen species found in some autonomic regulatory brain areas have been implicated in hypertension. However, a link between oxidative stress and peripheral chemoreflex integration within the RVLM has never been investigated. Here, we tested the hypothesis that the pressor response induced by peripheral chemoreflex activation involves the angiotensin-II/AT1R/superoxide pathway within the rostral ventrolateral medulla (RVLM). Seventeen male Wistar rats (260–300 g) were implanted with bilateral guide cannulae towards the RVLM and were fitted with catheters for blood pressure recordings and drug administration. Peripheral chemoreflex activation with potassium cyanide (80 μg/kg, i.v.) produced a transient increase in blood pressure, which was attenuated 2 minutes after bilateral microinjection of losartan (1 nmol), an AT1 receptor antagonist, in the RVLM (+ 54 ± 4 vs + 19 ± 3 Δmm Hg, P < 0.05, n = 6). Moreover, superoxide scavenging in the RVLM using a superoxide dismutase (SOD) mimetic, Tempol (5 nmol), significantly blunted the pressor response to peripheral chemoreflex activation (+ 50 ± 3 vs + 18 ± 3 Δmm Hg, P < 0.05, n = 7). On the other hand, bilateral microinjection of saline (n = 4) in the RVLM produced no change in the pressor response to chemoreflex activation. Taken together, these data suggest that the neurotransmission of the peripheral chemoreflex within the RVLM involves, at least in part, the activation of AT1 receptors and downstream superoxide formation.

Research Highlights
► Peripheral chemoreflex processing in the RVLM involves superoxide anions.
► Losartan microinjected in the RVLM attenuates peripheral chemoreflex responses.
► Tempol microinjected in the RVLM blunts peripheral chemoreflex responses.