Superoxide inhibits neuronal nitric oxide synthase influences on afferent arterioles in spontaneously hypertensive rats.
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.
Internal Medicine, Keio University School of Medicine, Tokyo, Japan.
A
A
Ichihara
M
M
Hayashi
N
N
Hirota
T
T
Saruta
D000818:Animals; D002956:Citrulline / Q000031:analogs & derivatives* / Q000494:pharmacology; D003497:Cyclic N-Oxides / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007606:Juxtaglomerular Apparatus / Q000187:drug effects* / Q000502:physiology; D008297:Male; D018715:Microscopy, Video; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D052248:Nitric Oxide Synthase Type I; D019335:Nitroarginine / Q000494:pharmacology; D010396:Penicillamine / Q000031:analogs & derivatives / Q000494:pharmacology; D010477:Perfusion; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D026423:S-Nitroso-N-Acetylpenicillamine; D013113:Spin Labels; D013481:Superoxides / Q000494:pharmacology*; D013890:Thiourea / Q000031:analogs & derivatives* / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects
D003497:Cyclic N-Oxides; D004791:Enzyme Inhibitors; D013113:Spin Labels; D013481:Superoxides; D019335:Nitroarginine; D002956:Citrulline; D026423:S-Nitroso-N-Acetylpenicillamine; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; C496322:Nos1 protein, rat; D010396:Penicillamine; D013890:Thiourea; C086717:S-methylthiocitrulline; C001803:tempol