ENDOTHELIAL NITRIC OXIDE SYNTHASE (eNOS) WITHIN THE PERIAQUEDUCTAL GRAY MATTER DIFFERENTIALLY MODULATES NEUROTRANSMISSION AND CARDIOVASCULAR RESPONSES DURING MECHANICAL, HEAT, AND COLD NOCICEPTION

Abstract

Nitric oxide (NO) is synthesized from L‐arginine via NO synthase (NOS) that exists as 3 isoforms: neuronal, inducible and endothelial (eNOS). We examined the role of eNOS within the periaqueductal gray mater (PAG) on cardiovascular responses and glutamate (GLU) and GABA concentrations during mechanical, thermal, and cold nociception to the hind paw in anesthetized rats. Mechanical stimulus (bilateral hindpaw pinch, 10 sec) increased mean arterial pressure (MAP), heart rate (HR), & GLU in PAG while GABA decreased. Bilateral microdialysis of a selective eNOS antagonist, 7‐nitroindazole (7‐NI; 1μM), into the PAG had no effect on MAP, HR, GLU & GABA during a mechanical stimulus. A heat stimulus (immersing a hindpaw metatarsus in water, 52°C, 10 sec) increased MAP, HR and GLU, while GABA decreased. Administration of 7‐NI into PAG augmented cardiovascular and GLU responses, and attenuated GABA changes. In contrast, a cold water stimulus (10°C, 10 sec) decreased MAP, HR, and GLU, but increased GABA. However, following microdialysis of 7‐NI into the PAG, a cold stimulus evoked pressor and tachycardic responses, augmented GLU and attenuated GABA levels. Results demonstrate that eNOS within the PAG plays a differential role in modulating cardiovascular responses and GLU/GABAergic neurotransmission during mechanical‐, heat‐, and cold‐mediated nociception.