Nitric oxide (NO) is essential for the normal functioning of the cardiovascular system. This study has determined whether chronic administration of L-arginine, the biological precursor of NO, attenuates the development of structural and functional changes in the hearts and blood vessels of deoxycorticosterone acetate (DOCA)-salt hypertensive rats. Uninephrectomised rats treated with DOCA (25mg every 4th day sc) and 1% NaCl in the drinking water for 4 weeks were treated with L-arginine (5% in food, 3.4±0.3 g/kg body weight/d). Changes in cardiovascular structure and function were determined by echocardiography, microelectrode studies, histology and studies in isolated hearts and thoracic aortic rings. DOCA-salt rats developed hypertension, left ventricular hypertrophy with an increased left ventricular wall thickness and decreased ventricular internal diameter, increased inflammatory cell infiltration, increased ventricular interstitial and perivascular collagen deposition, increased passive diastolic stiffness, prolonged action potential duration, increased oxidative stress and an inability to increase purine efflux in response to an increased workload. Administration of L-arginine markedly attenuated or prevented these changes. L-arginine treatment also normalised the reduced efficacy of noradrenaline and acetylcholine in isolated thoracic aortic rings of DOCA-salt rats. This study suggests that a functional NO deficit in blood vessels and the heart due to decreased NO synthase activity or increased release of reactive oxygen species such as superoxide may be a key change initiating many aspects of the cardiovascular impairment observed in DOCA-salt hypertensive rats. These changes can be prevented or attenuated by administration of L-arginine.