P108
This study was designed to determine the influence of increased superoxide anion production in neuronal nitric oxide synthase (nNOS)-dependent regulation of afferent arteriolar diameter in spontaneously hypertensive rats (SHR). Afferent arteriolar diameters of male Wister-Kyoto rats (WKY) and SHR (300-350 g) were assessed
in vitro
using the blood-perfused juxtamedullary nephron technique and averaged 21.6 ± 1.6 (n = 6) and 18.8 ± 1.2 μm (n = 7); respectively. Superfusion with the superoxide dismutase mimetic, tempol (1, 10, and 100 μmol/L), did not influence afferent arteriolar diameters 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), superfusion with the nNOS inhibitor,
S
-methyl-L-thiocitrulline (L-SMTC; 10 μmol/L), and the NOS inhibitor,
N
w
-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 treatment did not influence afferent arteriolar diameters (21.0 ± 1.5 μm), but L-NNA treatment exerted a significant afferent arteriolar constriction (14.8 ± 3.2%) which was similar to that observed in WKY. Experiments were also performed in the presence of 100 μmol/L tempol. In WKY (n = 6), tempol treatment did not modulate basal afferent arteriolar diameters (21.5 ± 1.2 μm) or afferent arteriolar constrictor responses to L-SMTC (10.6 ± 2.1%) and L-NNA (19.3 ± 3.3%). In SHR (n = 8), tempol treatment 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, superfusion with the nitric oxide donor,
S
-nitroso-N-acetylpenicillamine (10 μmol/L), which exerted a similar afferent arteriolar vasodilation (19.7 ± 3.8%, n = 4), did not influence afferent arteriolar responses to L-SMTC (-2.1 ± 3.1%) or L-NNA (15.1 ± 3.3%). These results suggest that increased superoxide anion inhibits nNOS-dependent regulation of afferent arteriolar diameters in SHR.
Superoxide Inhibits Neuronal Nitric Oxide Synthase Influences on Afferent Arterioles in Spontaneously Hypertensive Rats
