The myth of nitric oxide in central cardiovascular control by the nucleus tractus solitarii

Abstract

Considerable evidence suggests that nitroxidergic mechanisms in the nucleus tractus solitarii (NTS) participate in cardiovascular reflex control. Much of that evidence, being based on responses to nitric oxide precursors or inhibitors of nitric oxide synthesis, has been indirect and circumstantial. We sought to directly determine cardiovascular responses to nitric oxide donors microinjected into the NTS and to determine if traditional receptor mechanisms might account for responses to certain of these donors in the central nervous system. Anesthetized adult Sprague Dawley rats that were instrumented for recording arterial pressure and heart rate were used in the physiological studies. Microinjection of nitric oxide itself into the NTS did not produce any cardiovascular responses and injection of sodium nitroprusside elicited minimal depressor responses. The S-nitrosothiols, Snitrosoglutathione (GSNO), S-nitrosoacetylpenicillamine (SNAP), and S-nitroso-D-cysteine (D-SNC) produced no significant cardiovascular responses while injection of S-nitroso-L-cysteine (L-SNC) elicited brisk, dose-dependent depressor and bradycardic responses. In contrast, injection of glyceryl trinitrate elicited minimal pressor responses without associated changes in heart rate. It is unlikely that the responses to L-SNC were dependent on release of nitric oxide in that 1) the responses were not affected by injection of oxyhemoglobin or an inhibitor of nitric oxide synthesis prior to injection of L-SNC and 2) Land D-SNC released identical amounts of nitric oxide when exposed to brain tissue homogenates. Although GSNO did not independently affect blood pressure, its injection attenuated responses to subsequent injection of L-SNC. Furthermore, radioligand binding studies suggested that in rat brain synaptosomes there is a saturable binding site for GSNO that is displaced from that site by L-SNC. The studies suggest that S-nitrosocysteine, not nitric oxide, may be an interneuronal messenger for cardiovascular neurons in the NTS.

Central Control Mechanisms of Circulation in the Medulla Oblongata by Nitric Oxide.

“…Several investigators [57,[59][60][61][62][63][64][65][66][67][68][69][70][71] have reported data for the effects of microinjection of NO related substances into the NTS on circulation. In 1991, Lewis et al…”

“…Recently, Talman [69] published a paper entitled "The myth of nitric oxide in central cardiovascular control by the nucleus tractus solitarii." He and his colleagues [67,69] found that microinjection of L-Snitrosocysteine (L-SNC) into the NTS decreased the ABP in contrast to D-S-nitrosocysteine (D-SNC), which produced minimal responses, although L-and D-SNC released identical amounts of NO.…”

“…He and his colleagues [67,69] found that microinjection of L-Snitrosocysteine (L-SNC) into the NTS decreased the ABP in contrast to D-S-nitrosocysteine (D-SNC), which produced minimal responses, although L-and D-SNC released identical amounts of NO. These different responses to the two isomers cannot be explained by the extracellular release of NO.…”