Tempol attenuates excitatory actions of angiotensin II in the rostral ventrolateral medulla during emotional stress.
Superoxide has been shown to be an important intracellular mediator of actions of angiotensin II. Recently, we found that blockade of angiotensin II type-1 receptors in the rostral ventrolateral medulla (RVLM) abrogated the pressor effect of emotional stress in rabbits. In the present study, we examined the influence of superoxide dismutase mimetics, tempol and tiron, in RVLM on cardiovascular stress response in conscious rabbits. Air-jet stress evoked a sustained increase in blood pressure (+14+/-2 mm Hg), tachycardia (+52+/-7 bpm), and renal sympathoactivation (+58+/-8%). Bilateral microinjections of tempol or tiron (20 nmol) into RVLM did not alter resting cardiovascular parameters, but attenuated the pressor, sympathetic, and tachycardiac response to stress by 40% to 55%. By contrast, 3-carbamoylproxyl, which is structurally close to tempol but has a lower superoxide scavenging activity, did not alter the stress response. Neither tempol nor tiron altered the sympathoexcitatory response to glutamate microinjections into RVLM or to baroreceptor unloading. Microinjections of nitric oxide synthase inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME; 10 nmol) into RVLM did not affect the stress response. Coinjections of tempol and L-NAME decreased the pressor response to stress by 35+/-3%. Tempol attenuated the pressor response to microinjection of angiotensin II into RVLM by 59+/-15%, whereas L-NAME did not alter this response. These results suggest that superoxide dismutase mimetics in RVLM attenuate, partially via a nitric oxide-independent mechanism, the pressor effect of emotional stress in rabbits. Together with our previous studies, these results also indicate that superoxide is a key mediator of excitatory actions of angiotensin II in RVLM during acute stress.
Mayorov
Dmitry N
DN
Baker Heart Research Institute, PO Box 6492, St Kilda Rd Central, Melbourne, Victoria 8008, Australia. dmitry.mayorov@baker.edu.au
Head
Geoffrey A
GA
De Matteo
Robert
R
D000804:Angiotensin II / Q000378:metabolism*; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001794:Blood Pressure / Q000502:physiology; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D002320:Cardiovascular Physiological Phenomena; D003497:Cyclic N-Oxides / Q000494:pharmacology*; D016166:Free Radical Scavengers / Q000494:pharmacology*; D006439:Hemodynamics; D006973:Hypertension / Q000503:physiopathology; D009569:Nitric Oxide / Q000502:physiology; D011817:Rabbits; D013113:Spin Labels; D013312:Stress, Physiological / Q000503:physiopathology; D013315:Stress, Psychological / Q000503:physiopathology*; D013481:Superoxides / Q000494:pharmacology*; D013564:Sympathetic Nervous System / Q000502:physiology
D000975:Antioxidants; D003497:Cyclic N-Oxides; D016166:Free Radical Scavengers; D013113:Spin Labels; D013481:Superoxides; D000804:Angiotensin II; D009569:Nitric Oxide; C001803:tempol