Autocrine/paracrine modulation of baroreceptor activity after antidromic stimulation of aortic depressor nerve in vivo

Abstract

Activation of the sensory nerve endings of nonmyelinated C-fiber afferents evokes release of autocrine/paracrine factors that cause localized vasodilation, neurogenic inflammation, and modulation of sensory nerve activity. The aims of this study were to determine the effect of antidromic electrical stimulation on afferent baroreceptor activity in vivo, and investigate the role of endogenous prostanoids and hydrogen peroxide (H2O2) in mediating changes in nerve activity. Baroreceptor activity was recorded from the left aortic depressor nerve (ADN) in anesthetized rats before and after stimulating the ADN for brief (5–20 s) periods. The rostral end of the ADN was crushed or sectioned beforehand to prevent reflex changes in blood pressure. Antidromic stimulation of ADN using parameters that activate both myelinated A-fibers and nonmyelinated C-fibers caused pronounced and long-lasting (>1 min) inhibition of baroreceptor activity (n=9, P<0.05), with the magnitude and duration of inhibition dependent on the duration of the stimulation period (n=5). Baroreceptor activity was only transiently inhibited after selective stimulation of A-fibers. The inhibition of activity after antidromic stimulation of A and C fibers was prolonged after administration of the cyclooxygenase inhibitor indomethacin (5 mg/kg, IV, n=7) and abolished after administration of PEG-catalase (104 units/kg, IV, n=7), an enzyme that catalyzes the decomposition of H2O2 to water and oxygen. The results demonstrate a long-lasting inhibition of baroreceptor activity after antidromic stimulation of ADN and suggest that endogenous prostanoids and H2O2 oppose and mediate the inhibition, respectively. These mechanisms may contribute to rapid baroreceptor resetting during acute hypertension and be engaged during chronic baroreceptor activation therapy in patients with hypertension.

Ultrastructural Morphometry of the Aortic Depressor Nerves and Extrinsic Renal Nerves: Similarities and Differences between Mice and Rats

“…Reflex regulation of the circulation involving afferent nerves within the cardiovascular system has been widely investigated. The aortic depressor nerves (ADN) and extrinsic renal nerves (SRN) role in these reflexes have been stimulated and/or recorded in diverse experimental models [1][2][3][4]. The ADN are important baroreceptor afferences responsible for cardiovascular regulation, contributing for maintenance of the rapid changes in blood pressure, cardiovascular variability as well as modulation of central sympathetic outflow [5][6][7].…”