Effect of nuclear factor kappa B inhibition on L-NAME-induced hypertension and cardiovascular remodelling.
OBJECTIVE
We aimed to analyze effects of nuclear factor-kappa B (NF-kappaB) inhibition on blood pressure (BP) regulation and cardiovascular remodelling.


METHODS
Adult 12-week-old male Wistar Kyoto rats (WKY) were treated with the nitric oxide synthase (NOS) inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME, 40 mg/kg/day) for seven weeks. From the fourth week of L-NAME treatment, the NF-kappaB inhibitor lactacystin (1 microg/kg) was applied once a week. Furthermore, age-matched WKY received L-NAME or lactacystin alone for 7 or 3 weeks, respectively.


METHODS
Total NOS activity was determined in the left ventricle (LV) and aorta. The concentration of conjugated dienes, fibrosis, and collagen I and III levels were determined in the LV. The cross-sectional area (CSA) and wall thickness to internal diameter ratio (WT/ID) were measured in the aorta.


RESULTS
L-NAME treatment increased BP significantly (145 +/- 2 mmHg vs. 110 +/- 1 mmHg in controls). The addition of lactacystin resulted in further significant increase in BP (161 +/- 3 mmHg). Similarly, lactacystin potentiated the increased conjugated dienes concentration induced by L-NAME. Whereas L-NAME alone did not affect NOS activity, the addition of lactacystin decreased it in both tissues investigated. The addition of lactacystin did not affect LV hypertrophy, fibrosis, and collagen I and III, already increased by L-NAME; however, it further amplified CSA in the aorta increased by L-NAME alone. WT/ID increased significantly only after the addition of lactacystin.


CONCLUSIONS
Decreased NOS activity along with increased oxidative load may be responsible for decreased NO bio-availability and further BP increase after NF-kappaB inhibition in L-NAME-induced hypertension. Increased CSA and WT/ID could contribute to this hypertensive process.
Vrankova
Stanislava
S
Institute of Normal and Pathological Physiology and Centre of Excellence for Cardiovascular Research, Slovak Academy of Sciences, Sienkiewiczova 1, Bratislava, Slovak Republic. stanislava.vrankova@savba.sk
Parohova
Jana
J
Barta
Andrej
A
Janega
Pavol
P
Simko
Fedor
F
Pechanova
Olga
O
D000111:Acetylcysteine / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure; D006973:Hypertension / Q000139:chemically induced*; D008297:Male; D016328:NF-kappa B / Q000037:antagonists & inhibitors*; D019331:NG-Nitroarginine Methyl Ester / Q000009:adverse effects*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D051381:Rats; D011921:Rats, Inbred WKY; D020257:Ventricular Remodeling / Q000187:drug effects
D016328:NF-kappa B; C067713:lactacystin; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester; D000111:Acetylcysteine