Upregulation of vascular renin-angiotensin and endothelin systems in rats inhibited of nitric oxide synthesis.
The present study was aimed at investigating whether the regulation of vascular renin-angiotensin and endothelin (ET) systems is altered by a chronic blockade of nitric oxide (NO) synthesis. Male Sprague-Dawley rats were supplemented with N(G)-nitro-L-arginine methyl ester (L-NAME, 100mgl(-1)) in drinking water for 4 weeks to inhibit the endogenous synthesis of NO. The mRNA expressions of renin, angiotensin converting enzyme (ACE), type-1 angiotensin II receptor (AT1R), ET-1, type-A ET receptor (ET(A)), and neutral endopeptidase (NEP) were determined in the thoracic aorta by reverse transcription-polymerase chain reaction. The treatment with L-NAME significantly increased the blood pressure, while it decreased the tissue levels of nitrite/nitrate. The mRNA expression of renin, ACE, and AT1R was increased in the aorta. The protein expression of AT1R assessed by Western blot analysis was also increased. The expression of ET-1 and ET(A) mRNA was increased, whereas that of NEP mRNA decreased. The increased expression of renin-angiotensin and ET system genes and the decreased expression of NEP may in part be causally related with the development of hypertension induced by a chronic blockade of NO synthesis.
Lee
Jongun
J
Chonnam National University Research Institute of Medical and Dental Sciences, Gwangju 501-746, South Korea. julee@jnu.ac.kr
Kim
Sunmi
S
Oh
Yoonwha
Y
Ryu
Sun Youl
SY
Kim
Soo Wan
SW
D000818:Animals; D001013:Aorta, Thoracic / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D019332:Endothelin-1 / Q000096:biosynthesis / Q000235:genetics*; D015870:Gene Expression / Q000235:genetics; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000378:metabolism*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000037:antagonists & inhibitors*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D017466:Receptors, Endothelin / Q000096:biosynthesis / Q000235:genetics; D012084:Renin-Angiotensin System / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015854:Up-Regulation
D019332:Endothelin-1; D012333:RNA, Messenger; D017466:Receptors, Endothelin; D009569:Nitric Oxide; D019331:NG-Nitroarginine Methyl Ester