(Hypertension. 2001;37:630.)
© 2001 American Heart Association, Inc.
Scientific Contributions |
From the Internal Medicine, Keio University School of Medicine, Tokyo, Japan.
Correspondence to Dr Takao Saruta, Department of Internal Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan. E-mail saruta{at}med.keio.ac.jp
This
study was designed to determine the influence of increased superoxide
anion in neuronal nitric oxide synthase (nNOS)-dependent regulation of
afferent arterioles in spontaneously hypertensive rats (SHR). Afferent
arteriolar diameters of male Wistar-Kyoto rats (WKY) and SHR were
assessed in vitro with the blood-perfused juxtamedullary nephron
technique and averaged 21.6±1.6 (n=6) and 18.8±1.2 (n=7) µm,
respectively. The superoxide dismutase mimetic Tempol (1, 10, and 100
µmol/L) did not influence afferent arterioles of WKY but
significantly increased afferent arteriolar diameters of SHR by
20.6±5.5%, 25.2±5.4%, and 23.3±4.9%, respectively. In WKY (n=6),
the nNOS inhibitor
S-methyl-L-thiocitrulline
(L-SMTC; 10 µmol/L) and the NOS inhibitor
N
-nitro-L-arginine
(L-NNA; 100 µmol/L) significantly decreased afferent arteriolar
diameters (19.6±1.6 µm) by 11.9±3.1% and 21.0±3.9%,
respectively. In SHR (n=7), L-SMTC did not influence afferent
arteriolar diameters (21.0±1.5 µm), but L-NNA exerted an afferent
arteriolar constriction (14.8±3.2%) that was similar to the response
observed in WKY. Experiments were also performed in the presence of 100
µmol/L Tempol. In afferent arterioles of WKY (n=6), Tempol treatment
did not modulate the basal diameters (21.5±1.2 µm) or the
constrictor response to L-SMTC (10.6±2.1%) or L-NNA (19.3±3.3%). In
SHR (n=8), Tempol significantly increased afferent arteriolar diameters
by 22.5±4.3% and enhanced afferent arteriolar constrictor responses
to L-SMTC (18.4±2.7%) and L-NNA (31.9±2.6%). However, the nitric
oxide donor
S-nitroso-N-acetylpenicillamine
(10 µmol/L), which similarly increased afferent arteriolar diameters
(17.2±2.3%, n=6), did not affect afferent arteriolar responses to
L-SMTC (1.5±2.7%) or L-NNA (18.6±2.3%). These suggest that
superoxide anion inhibits the control of afferent arteriolar diameters
by nNOS in SHR.
Key Words: Tempol nitric oxide synthase arterioles rats, spontaneously hypertensive kidney
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