Endogenous nitric oxide derived from NOS I or II in thoracic spinal cord exerts opposing tonic modulation on sympathetic vasomotor tone via disparate mechanisms in anesthetized rats

Abstract

The sympathetic preganglionic neurons (SPN) in the thoracic spinal cord regulate vasomotor tone via norepinephrine released from sympathetic terminals and adrenal medulla. We assessed the hypothesis that nitric oxide synthase I (NOS I)- and NOS II-derived nitric oxide (NO) in the thoracic spinal cord differentially modulate sympathetic outflow and that the adrenal medulla may be involved in those modulatory actions. In Sprague-Dawley rats, NOS I immunoreactivity was distributed primarily in the perikaryon, proximal dendrites, or axons of SPN, and small clusters of NOS II immunoreactivity impinged mainly on the circumference of SPN. Intrathecal administration of 7-nitroindazole (7-NI), a specific NOS I antagonist, into the thoracic spinal cord significantly reduced arterial pressure, heart rate, and basal or baroreflex-mediated sympathetic vasomotor tone. On the other hand, intrathecal application of S-methylisothiourea (SMT), a specific NOS II antagonist, elevated arterial pressure with a transient reduction of heart rate, induced a surge of plasma norepinephrine, and reduced baroreflex-mediated but not basal sympathetic vasomotor tone. Bilateral adrenalectomy significantly exacerbated the cardiovascular responses to 7-NI but antagonized those to SMT. We conclude that both NOS I and NOS II are present in the thoracic spinal cord and are tonically active under physiological conditions. Furthermore, the endogenous NO generated by NOS I-containing SPN exerts a tonic excitatory action on vasomotor tone mediated by norepinephrine released from the adrenal medulla and sympathetic nerve terminals. On the other hand, NO derived from NOS II exerts a tonic inhibitory action on sympathetic outflow from the SPN that targets primarily the blood vessels.

Nitric Oxide Orchestrates a Power-Law Modulation of Sympathetic Firing Behaviors in Neonatal Rat Spinal Cords

“…Moreover, intrathecal Arg maintains mean blood pressure during hemorrhage in anesthetized rats (Malik et al, 2007 ). While these findings support a hypothetical NO-mediated activation of vasomotor tone in the spinal cord, a recent study demonstrates that NO produced by NOS-I in SPNs contributes to maintain while NO produced by NOS-II in the vicinity of the intermediate lateral cell column tonically depress mean arterial blood pressure (Poon et al, 2016 ). By direct neural recordings, it has been demonstrated that intrathecal Arg increases renal sympathetic nerve activities in anesthetized rabbits (Hakim et al, 1995 ).…”

Activation of spinal nociceptin receptors induces cardiovascular depression and antinociception in an independent manner in mice

“…Intrathecal administration of nociceptin (1, 2, or 5 nmol) in ICR mice elicited a significant and dose-dependent decrease in MAP and HR over our 60 minute observation period ( Figure 2 ). The power density of the low-frequency (BLF) component of SBP spectrum, an experimental index for spontaneous baroreflex-mediated sympathetic vasomotor tone, 30 – 33 also underwent a dose-dependent reduction over a time course that paralleled the changes in MAP. At the same time, the BRS, an experimental index for spontaneous cardiac vagal baroreflex, 31 , 34 exhibited a dose-dependent increase that mirrored the decrease in HR.…”

“…The recorded BP signals from the femoral artery were processed by an arterial BP analyzer (Notocord, Croissy-Sur-Seine, France) and the systolic blood pressure (SBP) signals were simultaneously subject to online and real-time spectral analysis (Notocord) to detect the power density of the low-frequency component of SBP spectrum (BLF; 0.15–0.6 Hz). 30 , 31 The power density of this spectral band has been demonstrated to be a valid experimental index for spontaneous baroreflex-mediated sympathetic vasomotor tone. 30 – 33 To evaluate the spontaneous cardiac vagal baroreflex, we employed a baroreflex sequence analyzer (Notocord) to determine baroreflex sensitivity (BRS) based on online detection of spontaneous sequences of consecutive increases or decreases in SBP associated with parallel changes in HR.…”

“… 30 , 31 The power density of this spectral band has been demonstrated to be a valid experimental index for spontaneous baroreflex-mediated sympathetic vasomotor tone. 30 – 33 To evaluate the spontaneous cardiac vagal baroreflex, we employed a baroreflex sequence analyzer (Notocord) to determine baroreflex sensitivity (BRS) based on online detection of spontaneous sequences of consecutive increases or decreases in SBP associated with parallel changes in HR. 31 , 34 With reference to Laude et al, 33 the settings were analysis window: 60 seconds; synchronization delay: three cycles; and minimum sequence length: three cycles.…”

Activation of spinal nociceptin receptors induces cardiovascular depression and antinociception in an independent manner in mice

“…The recorded BP signals from the femoral artery were processed by an arterial BP analyzer (Notocord, Croissy-Sur-Seine, France) and the systolic blood pressure (SBP) signals were simultaneously subject to online and real-time spectral analysis (Notocord) to detect the power density of the low-frequency component of SBP spectrum (BLF; 0.15-0.6 Hz). 30,31 The power density of this spectral band has been demonstrated to be a valid experimental index for spontaneous baroreflex-mediated sympathetic vasomotor tone. [30][31][32][33] To evaluate the spontaneous cardiac vagal baroreflex, we employed a baroreflex sequence analyzer (Notocord) to determine baroreflex sensitivity (BRS) based on online detection of spontaneous sequences of consecutive increases or decreases in SBP associated with parallel changes in HR.…”