Role of the spinal cord NO/cGMP pathway in the control of arterial pressure and heart rate

Abstract

The modulatory effect of nitric oxide/cyclic guanosine monophosphate (NO/cGMP) pathway on sympathetic preganglionic neurons still deserves further investigation. The present study was designed to examine the role of the spinal cord NO/cGMP pathway in controlling mean arterial pressure and heart rate. We observed that intrathecal administration of the NO synthase inhibitor Nω-Nitro-L-arginine methyl ester hydrochloride (L-NAME) causes an increase in mean arterial pressure but does not affect heart rate. Intrathecal administration of the soluble guanylyl cyclase inhibitor 1H-[1,2,4]Oxadiazolo[4,3-a]quinoxalin-1-one (ODQ) does not change mean arterial pressure and heart rate. The precursor for NO synthesis, L-arginine, reduces both mean arterial pressure and heart rate while administration of ODQ before L-arginine impaired decreases in mean arterial pressure and heart rate. Administration of the N-methyl-D-aspartate (NMDA) receptor antagonist DL-2-amino-5-phosphonopentanoic acid (AP5) after L-NAME does not affect increases in mean arterial pressure promoted by NO synthase inhibition. Although the hypotensive and bradycardic responses induced by intrathecal administration of L-arginine depend on cGMP, our results indicate that NO acts to tonically inhibit SPNs, independent of either cGMP or NMDA receptors.

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

“…Although not without debate, the sympathetic outflows supplying the cardiovascular systems are predominantly reduced by NO production in the spinal cord, as inferred by observing changes in systemic arterial blood pressure (Iida, 1999 ; Arnolda et al, 2000 ; Sabino et al, 2011 ). Consistent with this view, intrathecal L-NAME increases blood pressure in both conscious rats (Lu et al, 1999 ) and anesthetized rats (Koga et al, 1999 ).…”

The NO-cGMP-PKG Axis in HFpEF: From Pathological Mechanisms to Potential Therapies

“…NO exerts its physiological functions through the cGMP-independent pathway and the cGMP-dependent pathway that is mediated by activation of sGC [28]. Catalysis of sCG induces an increase in the intracellular concentrations of cGMP and its downstream effector PKG, which underlies their diverse biological functions, such as mediation of vascular smooth muscle cell relaxation, inhibition of platelet aggregation, and participation in neurotransmission [34,35].…”