Effect of chronic apocynin treatment on nitric oxide and reactive oxygen species production in borderline and spontaneous hypertension.
The purpose of this study was to investigate the effect of NAD(P)H oxidase inhibitor - apocynin (4-hydroxy-3-methoxyacetophenone) on the increase of systolic blood pressure (SBP) in borderline (BHR) and spontaneously hypertensive rats (SHR). Young 6-week-old male BHR (offspring of SHR dams and Wistar Kyoto sires) and SHR were treated with apocynin (30 mg/kg/day) for six weeks. SBP was measured by tail-cuff plethysmography. Nitric oxide synthase (NOS) activity was determined in the left ventricle and aorta. Protein expression of nuclear factor kappa B (NF-kappaB) and NAD(P)H oxidase subunits p67phox and p22phox as well as concentration of cGMP were determined for the left ventricle. Apocynin significantly decreased SBP in all groups investigated. Administration of apocynin had no effect on NOS activity in either tissue studied. However, apocynin decreased protein expression of NF-kappaB (p65) and NAD(P)H oxidase subunit p22phox in both hypertensive groups and p67phox subunit in the SHR group. Moreover, apocynin was able to prevent a decrease in cGMP concentration in the left ventricle of both hypertensive groups. In conclusion, our study demonstrated that apocynin treatment partially prevented SBP rise in borderline and spontaneously hypertensive rats, yet without increasing activity of NOS in the left ventricle and aorta. However, apocynin was able to decrease production of reactive oxygen species in hypertensive rats; thus preventing the decrease in cGMP formation.
Pechánová
Olga
O
Institute of Normal and Pathological Physiology, Center of Excellence for Cardiovascular Research, Slovak Academy of Sciences, Sienkiewiczova 1, Bratislava, Slovak Republic. olga.pechanova@savba.sk
Jendeková
Lýdia
L
Vranková
Stanislava
S
D000098:Acetophenones / Q000494:pharmacology*; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D006152:Cyclic GMP / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects; D006973:Hypertension / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D019255:NADPH Oxidases / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000235:genetics; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D017382:Reactive Oxygen Species / Q000378:metabolism; D051996:Transcription Factor RelA / Q000187:drug effects / Q000235:genetics
D000098:Acetophenones; D000975:Antioxidants; D004791:Enzyme Inhibitors; D017382:Reactive Oxygen Species; D051996:Transcription Factor RelA; D009569:Nitric Oxide; C056165:acetovanillone; D019001:Nitric Oxide Synthase; D019255:NADPH Oxidases; C515768:Cyba protein, rat; D006152:Cyclic GMP