Nitric oxide synthase inhibition in rostral ventrolateral medulla attenuates pressor response to psychological stress in rabbits.
Nitric oxide (NO) has been critically implicated in the central regulation of autonomic function. We recently found, however, that acute (up to 30min) blockade of NO synthase (NOS) in the rostral ventrolateral medulla (RVLM) inhibited sympathetic baroreflex transmission, without altering the cardiovascular response to psychological (air-jet) stress in rabbits. In the present study, we examined the effect of the later phase (1-3h) of NOS inhibition in the RVLM on the pressor and sympathetic responses to air-jet stress in conscious rabbits. Air-jet evoked a sustained increase in blood pressure (+14+/-2mmHg), heart rate (+37+/-9beats/min) and renal sympathetic nerve activity (+52+/-8%). Bilateral microinjection of a NOS inhibitor l-NAME (10nmol) into RVLM did not affect resting parameters or stress responses during the first 30min after injection. Conversely, in the later phase of NOS inhibition, the pressor, tachycardic and renal sympathetic responses to air-jet stress were reversibly attenuated by 48-72%. Microinjection of l-NAME outside the RVLM did not change stress responses. Microinjection of glutamate (3nmol) into the RVLM induced similar pressor effects before and after l-NAME (+30+/-6mmHg and +26+/-6mmHg, respectively). Microinjection of d-NAME altered neither stress responses nor pressor response to glutamate. These results suggest that NOS inhibition in the RVLM has a dual effect on the autonomic response to psychological stress. In the early phase, NOS inhibition has little impact on this response. However, in the later phase, NOS inhibition attenuates the stress response, perhaps via indirect mechanisms such as altering the local redox state.
Mayorov
Dmitry N
DN
Baker Heart Research Institute, Melbourne, Victoria, Australia. dmitry.mayorov@baker.edu.au
D000818:Animals; D001522:Behavior, Animal; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D008526:Medulla Oblongata / Q000187:drug effects / Q000378:metabolism*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D011817:Rabbits; D013315:Stress, Psychological / Q000473:pathology* / Q000503:physiopathology*
D004791:Enzyme Inhibitors; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester