Increased basal nitric oxide release despite enhanced free radical production in hypertension.
BACKGROUND
Although in hypertension a defect in stimulated nitric oxide (NO) is well established, little is known about basal NO levels. Thus, we measured directly in vessels from normotensive [Wistar-Kyoto (WKY)] rats and spontaneously hypertensive rats (SHR) both basal and stimulated NO production using a novel technique [4,5-diaminofluorescein (DAF-2) fluorescence].


METHODS
Isolated vessels were exposed to the fluorescent probe DAF-2. After the technique was validated with increasing doses of acetylcholine in the presence and absence of NG-nitro-L-arginine methyl ester (l-NAME), we measured NO production in vessels from WKY rats and SHR in the same experimental setting. Finally, to explore the impact of reactive oxygen species (ROS) on NO release, we analysed the effect of an antioxidant, such as ascorbic acid, on basal and stimulated NO in aortic rings of WKY rats and SHR.


RESULTS
Aortic rings from SHR exhibited a higher basal NO production and a lower responsiveness to agonist-induced NO release as compared with those observed in WKY rats. Also in resistance vessels such as mesenteric arteries, basal NO production was higher in hypertension. In hypertensive rats, ascorbic acid was able to further increase basal NO release and recovered the impaired stimulated NO production, whereas no effect was detected in normotensive rats.


CONCLUSIONS
Our data reveal an increased basal NO availability in hypertension despite the increased production of ROS, suggesting a greater complexity in hypertensive endothelial dysfunction when the analysis is focused on direct NO measurement.
Maffei
Angelo
A
IRCCS 'NEUROMED', Pozzilli (IS), Italy.
Poulet
Roberta
R
Vecchione
Carmine
C
Colella
Salvatore
S
Fratta
Luigi
L
Frati
Giacomo
G
Trimarco
Valentina
V
Trimarco
Bruno
B
Lembo
Giuseppe
G
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D001011:Aorta / Q000187:drug effects / Q000378:metabolism; D001205:Ascorbic Acid / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D019793:Fluorescein; D006973:Hypertension / Q000378:metabolism*; D066298:In Vitro Techniques; D007202:Indicators and Reagents; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects / Q000378:metabolism; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D017382:Reactive Oxygen Species / Q000378:metabolism*
C111205:4,5-diaminofluorescein; D000975:Antioxidants; D004791:Enzyme Inhibitors; D007202:Indicators and Reagents; D017382:Reactive Oxygen Species; D009569:Nitric Oxide; D000109:Acetylcholine; D001205:Ascorbic Acid; D019793:Fluorescein; D019331:NG-Nitroarginine Methyl Ester