Role of nNOS/sGC pathway in the insular cortex in control of cardiovascular, autonomic and corticosterone responses to restraint stress in rats.

The insular cortex (IC) is part of brain networks involved in physiological responses to stressful events. However, the local neurochemical mechanisms involved in the processing of stress responses by IC are still poorly understood. Thus, we investigated the involvement of nitrergic neurotransmission within the IC acting via neuronal isoform of nitric oxide synthase (nNOS), as well as its primary downstream target, soluble guanylate cyclase (sGC), in physiological responses during acute restraint stress, with a particular emphasis on cardiovascular and autonomic responses. For this, the selective nNOS inhibitor N(ω)propyl-L-arginine hydrochloride (NPLA, 0.04 nmol/100 nL), the NO scavenger carboxy-PTIO (1 nmol/100 nL) or the selective sGC inhibitor ODQ (1 nmol/100 nL) were bilaterally microinjected into the IC before restraint stress. We observed that the pressor and tachycardic responses to restraint were enhanced in animals treated with either NPLA, carboxy-PTIO or ODQ in the IC. Increase in circulating corticosterone during restraint was reduced in animals that received NPLA or carboxy-PTIO microinjections, but ODQ did not affect this neuroendocrine effect. Restraint-evoked drop in tail skin temperature was not affected by any of the IC pharmacological treatments. Overall, our findings provide evidence of an inhibitory influence of IC nNOS/sGC pathway in cardiovascular responses to restraint stress, whereas nNOS present within the IC is involved in corticosterone release into the circulation through sGC-independent mechanisms.