Acute pressor effect of central angiotensin II is mediated by NAD(P)H-oxidase-dependent production of superoxide in the hypothalamic cardiovascular regulatory nuclei.
BACKGROUND
Centrally applied angiotensin II (Ang II) increases sympathetic nervous activity and mean arterial blood pressure (MAP), but the mediation of these effects is not fully understood.


OBJECTIVE
To test the hypothesis that central effects of Ang II are mediated by reduced nicotinamide adenine dinucleotide phosphate [NAD(P)H]-oxidase-dependent production of superoxide in the hypothalamus.


METHODS
Under isoflurane anesthesia, male Sprague-Dawley rats were given an intracerebroventricular infusion of either artificial cerebrospinal fluid or apocynin (4 microg/kg per min), a selective inhibitor for NAD(P)H oxidase, for 30 min, followed by Ang II (20 ng) or carbachol (200 ng), while MAP and heart rate were measured at the femoral artery. At the end of the experiments, hydroethidine, a superoxide-sensitive fluorescent dye, was infused intravenously for 10 min, and superoxide production was assessed in the vasoregulatory hypothalamic nuclei using confocal microscopy.


RESULTS
Ang II elicited a rapid 11 +/- 2-mmHg increase in MAP and a 16 +/- 2-beats/min decrease in heart rate. Apocynin abolished these effects of Ang II in a specific manner, as carbachol-induced increases in MAP were unaffected by the inhibition of NAD(P)H oxidase (MAP increased by 9 +/- 2 and 8 +/- 1 mmHg in the absence and presence of apocynin, respectively). In response to Ang II, apocynin-sensitive production of superoxide increased significantly in the nuclei of the anterior hypothalamus, in the subfornical organ, and in the paraventricular nucleus of the hypothalamus.


CONCLUSIONS
These findings demonstrate that acute pressor responses of central Ang II are mediated by NAD(P)H-oxidase-dependent production of superoxide in the hypothalamus.
Erdös
Benedek
B
Geriatric Research, Education and Clinical Center, Department of Veterans Affairs Medical Center, Gainesville, Florida, USA. erdos@ufl.edu
Broxson
Christopher S
CS
King
Michael A
MA
Scarpace
Philip J
PJ
Tümer
Nihal
N
D000098:Acetophenones / Q000494:pharmacology; D000804:Angiotensin II / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D007025:Anterior Hypothalamic Nucleus / Q000187:drug effects / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects* / Q000502:physiology; D002217:Carbachol / Q000494:pharmacology; D002320:Cardiovascular Physiological Phenomena / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D018613:Microscopy, Confocal; D008856:Microscopy, Fluorescence; D019255:NADPH Oxidases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D010286:Paraventricular Hypothalamic Nucleus / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013356:Subfornical Organ / Q000187:drug effects / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism*; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000502:physiology
D000098:Acetophenones; D013481:Superoxides; D000804:Angiotensin II; D002217:Carbachol; C056165:acetovanillone; D019255:NADPH Oxidases