UPREGULATION OF VASCULAR RENIN–ANGIOTENSIN AND ENDOTHELIN SYSTEMS IN RATS INHIBITED OF NITRIC OXIDE SYNTHESIS

Abstract

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, 100 mg l −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.