Expression of NAD(P)H oxidase subunits and their contribution to cardiovascular damage in aldosterone/salt-induced hypertensive rat.
NAD(P)H oxidase plays an important role in hypertension and its complication in aldosterone-salt rat. We questioned whether NAD(P)H oxidase subunit expression and activity are modulated by aldosterone and whether this is associated with target-organ damage. Rats were infused with aldosterone (0.75 microg/hr/day) for 6 weeks and were given 0.9% NaCl+/-losartan (30 mg/kg/day), spironolactone (200 mg/kg/day), and apocynin (1.5 mM/L). Aldosterone-salt hypertension was prevented completely by spironolactone and modestly by losartan and apocynin. Aldosterone increased aortic NAD(P)H oxidase activity by 34% and spironolactone and losartan inhibited the activity. Aortic expression of the subunits p47(phox), gp91(phox), and p22(phox) increased in aldosterone-infused rats by 5.5, 4.7, and 3.2-fold, respectively, which was decreased completely by spironolactone and partially by losartan and apocynin. Therefore, the increased expression of NAD(P)H oxidase may contribute to cardiovascular damage in aldosterone-salt hypertension through the increased expression of each subunit.
Park
Young Mee
YM
Samsung Biomedical Research Institutue, Ottawa Health Research Institute, University of Ottawa, Ottawa, Canada.
Lim
Bong Hee
BH
Touyz
Rhian M
RM
Park
Jeong Bae
JB
D000098:Acetophenones / Q000008:administration & dosage; D000450:Aldosterone / Q000008:administration & dosage / Q000633:toxicity*; D047228:Angiotensin II Type 1 Receptor Blockers / Q000008:administration & dosage; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage; D001011:Aorta / Q000378:metabolism / Q000473:pathology; D001794:Blood Pressure / Q000187:drug effects; D006973:Hypertension / Q000139:chemically induced / Q000188:drug therapy / Q000201:enzymology*; D007668:Kidney / Q000378:metabolism / Q000473:pathology; D019808:Losartan / Q000008:administration & dosage; D008297:Male; D000451:Mineralocorticoid Receptor Antagonists / Q000008:administration & dosage; D019255:NADPH Oxidases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009929:Organ Size; D018384:Oxidative Stress; D021122:Protein Subunits / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012965:Sodium Chloride / Q000008:administration & dosage; D013148:Spironolactone / Q000008:administration & dosage; D013481:Superoxides / Q000378:metabolism
D000098:Acetophenones; D047228:Angiotensin II Type 1 Receptor Blockers; D000894:Anti-Inflammatory Agents, Non-Steroidal; D000451:Mineralocorticoid Receptor Antagonists; D021122:Protein Subunits; D012333:RNA, Messenger; D013481:Superoxides; D013148:Spironolactone; D012965:Sodium Chloride; D000450:Aldosterone; C056165:acetovanillone; D019255:NADPH Oxidases; D019808:Losartan