Effects of chronic inhibition of inducible nitric oxide synthase in hyperthyroid rats.
We hypothesized that nitric oxide generated by inducible nitric oxide synthase (iNOS) may contribute to the homeostatic role of this agent in hyperthyroidism and may, therefore, participate in long-term control of blood pressure (BP). The effects of chronic iNOS inhibition by oral aminoguanidine (AG) administration on BP and morphological and renal variables in hyperthyroid rats were analyzed. The following four groups (n = 8 each) of male Wistar rats were used: control group and groups treated with AG (50 mg.kg(-1).day(-1), via drinking water), thyroxine (T4, 50 microg.rat(-1).day(-1)), or AG + T4. All treatments were maintained for 3 wk. Tail systolic BP and heart rate (HR) were recorded weekly. Finally, we measured BP (mmHg) and HR in conscious rats and morphological, plasma, and renal variables. T(4) administration produced a small BP (125 +/- 2, P < 0.05) increase vs. control (115 +/- 2) rats. AG administration to normal rats did not modify BP (109 +/- 3) or any other hemodynamic variable. However, coadministration of T4 and AG produced a marked increase in BP (140 +/- 3, P < 0.01 vs. T4). Pulse pressure and HR were increased in both T4- and T4 + AG -treated groups without differences between them. Plasma NOx (micromol/l) were increased in the T4 group (10.02 +/- 0.15, P < 0.05 vs. controls 6.1 +/- 0.10), and AG reduced this variable in T4-treated rats (6.81 +/- 0.14, P < 0.05 vs. T4) but not in normal rats (5.78 +/- 0.20). Renal and ventricular hypertrophy and proteinuria of hyperthyroid rats were unaffected by AG treatment. In conclusion, the results of the present paper indicate that iNOS activity may counterbalance the prohypertensive effects of T4.
Rodríguez-Gómez
Isabel
I
Facultad de Medicina, Departamento de Fisiología, E-18012 Granada, Spain.
Wangensteen
Rosemary
R
Moreno
Juan Manuel
JM
Chamorro
Virginia
V
Osuna
Antonio
A
Vargas
Félix
F
D000818:Animals; D001774:Blood Chemical Analysis; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006146:Guanidines / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects; D006980:Hyperthyroidism / Q000201:enzymology* / Q000503:physiopathology; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D009929:Organ Size / Q000187:drug effects; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D013974:Thyroxine / Q000378:metabolism; D016482:Urinalysis
D004791:Enzyme Inhibitors; D006146:Guanidines; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D013974:Thyroxine; C004479:pimagedine