Central infusion of L-arginine or superoxide dismutase does not alter arterial pressure in SHR.
Cardiovascular responses to L-arginine and nitric oxide (NO) are augmented in the rostral ventrolateral medulla (RVLM) of spontaneously hypertensive rats (SHR), and the intravenous injection of superoxide dismutase (SOD) mimetic decreases the arterial pressure in these rats. In the present study, we examined whether the chronic central infusion of L-arginine or an SOD mimetic would reduce the blood pressure of SHR and alter responses to an NOS inhibitor or an NO donor in the RVLM. For this purpose, we administered L-arginine (SHR-Arg: 13.2 micromol/day, n=6), a stable membrane-permeable SOD mimetic, 4-hydroxy-2, 2,6,6-tetramethyl piperidine-1-oxyl (tempol) (SHR-Temp: 13.2 micromol/day, n=6), or vehicle (SHR-C: n=6) into the lateral ventricle of 12-week-old SHR for 2 weeks. When the rats reached 14 weeks of age, N(G)-nitro-L-arginine methyl ester (L-NAME: 10 nmol/50 nl) or NOC 18 (NO donor: 10 nmol/50 nl) was microinjected into the unilateral RVLM. Blood pressure did not decrease in any of the treatment groups (SHR-Arg: 209+/-4 mmHg, SHR-Temp: 210+/-6 mmHg, SHR-C: 197+/-6 mmHg). The microinjection of L-NAME into the RVLM induced a significant increase in the mean arterial pressure (MAP) (SHR-Arg: 10-4 mmHg, SHR-Temp: 12+/-4 mmHg, SHR-C: 11+/-3 mmHg), and the increases in MAP did not differ among the groups. The micro-injection of NOC 18 reduced MAP (SHR-Arg: -12+/-2 mmHg, SHR-Temp: -15+/-3 mmHg, SHR-C: -13+/-3 mmHg), and the depressor responses were comparable among groups. These results do not support the hypothesis that chronic L-arginine deficiency or the enhanced degeneration of NO by superoxide radicals in the central nervous system contributes to the maintenance of arterial pressure in SHR.
Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
S
S
Kagiyama
T
T
Tsuchihashi
I
I
Abe
K
K
Matsumura
M
M
Fujishima
D000818:Animals; D001120:Arginine / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects*; D003497:Cyclic N-Oxides / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D016166:Free Radical Scavengers / Q000494:pharmacology; D006973:Hypertension / Q000503:physiopathology*; D007260:Infusion Pumps; D007276:Injections, Intraventricular; D008297:Male; D008526:Medulla Oblongata / Q000187:drug effects / Q000503:physiopathology; D008845:Microinjections; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D020030:Nitric Oxide Donors / Q000494:pharmacology; D009603:Nitroso Compounds / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR / Q000502:physiology*; D013113:Spin Labels; D013482:Superoxide Dismutase / Q000494:pharmacology*
D003497:Cyclic N-Oxides; D004791:Enzyme Inhibitors; D016166:Free Radical Scavengers; C093285:NOC 18; D020030:Nitric Oxide Donors; D009603:Nitroso Compounds; D013113:Spin Labels; D001120:Arginine; D013482:Superoxide Dismutase; C001803:tempol; D019331:NG-Nitroarginine Methyl Ester