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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) micrometer, respectively. The superoxide dismutase mimetic Tempol (1, 10, and 100 micromol/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 micromol/L) and the NOS inhibitor N(omega)-nitro-L-arginine (L-NNA; 100 micromol/L) significantly decreased afferent arteriolar diameters (19.6+/-1.6 micrometer) 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 micrometer), 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 micromol/L Tempol. In afferent arterioles of WKY (n=6), Tempol treatment did not modulate the basal diameters (21.5+/-1.2 micrometer) 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 micromol/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.

Superoxide Inhibits Neuronal Nitric Oxide Synthase Influences on Afferent Arterioles in Spontaneously Hypertensive Rats