Increased oxidative stress impairs endothelial modulation of contractions in arteries from spontaneously hypertensive rats.
OBJECTIVE
The endothelium modulates vascular contractions. We investigated the effects of oxidative stress on endothelial modulation of contractions in hypertension.


METHODS
Changes in isometric tension of femoral arterial rings from spontaneously hypertensive (SHR) and Wistar-Kyoto (WKY) rats were recorded.


RESULTS
The contractile response to norepinephrine of arteries with endothelium was greater in SHR than in WKY rats (P < 0.0001). Endothelium removal augmented the norepinephrine-induced contraction (P < 0.05). The augmentation was more pronounced in WKY than in SHR, which resulted in comparable contraction of arteries without endothelium in both strains. Nomega-nitro-L-arginine methyl ester (100 micromol/l) mimicked the effect of endothelium removal. Production of nitric oxide (NO, assessed by measuring nitrite/nitrate concentrations) during the contraction was not different between SHR and WKY. Vitamin C suppressed the contraction of arteries with endothelium from SHR but not from WKY (P < 0.05). Diphenyleneiodonium and apocynin, inhibitors of nicotinamide adenine dinucleotide/nicotinamide adenine dinucleotide phosphate (NADH/NADPH) oxidase, attenuated the contraction of arteries with endothelium from SHR (P < 0.001) but not WKY, but did not affect contractions induced by serotonin. Superoxide generated by xanthine oxidase/hypoxanthine enhanced the norepinephrine-induced contraction of arteries with endothelium from WKY (P < 0.0001), and this effect was reversed by vitamin C.


CONCLUSIONS
In rat femoral arteries, NO released from the endothelium modulates vascular contraction. In SHR, production of superoxide by NADH/NADPH oxidase, which may be activated by norepinephrine, is enhanced, resulting in the inactivation of NO and impairment of endothelial modulation of vascular contractions. Vascular oxidative stress may contribute to the altered circulation in hypertension by impairing endothelial modulation of vascular contractions.
Miyagawa
Koichi
K
Department of Internal Medicine, Nagoya Koseiin Geriatric Hospital, Nagoya, Japan.
Ohashi
Masuo
M
Yamashita
Sumiyo
S
Kojima
Masayoshi
M
Sato
Koichi
K
Ueda
Ryuzo
R
Dohi
Yasuaki
Y
D000818:Animals; D004730:Endothelium, Vascular / Q000378:metabolism*; D005263:Femoral Artery / Q000502:physiology*; D066298:In Vitro Techniques; D008297:Male; D019255:NADPH Oxidases / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism*; D009638:Norepinephrine / Q000502:physiology*; D018384:Oxidative Stress / Q000502:physiology*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D013481:Superoxides / Q000378:metabolism; D014661:Vasoconstriction / Q000502:physiology*
D013481:Superoxides; D009569:Nitric Oxide; D019255:NADPH Oxidases; D009638:Norepinephrine