Background The renin-angiotensin system and endothelium-derived nitric oxide (EDNO) are important regulators of vascular tone. This study was designed to investigate endothelial and vascular smooth muscle function in coronary arteries of Ren-2 transgenic rats.Methods and Results Left anterior descending coronary arteries and aortas were isolated from transgenic rats and Sprague-Dawley control rats at 6 (young) and 12 (adult) weeks of age and examined in myographs or organ chambers for isometric tension recording. Systolic blood pressure was significantly higher in transgenic rats (young, 229+-6 mm Hg; adult, 239+-8 mm Hg) than in control rats (young, 126+-2 mm Hg; adult, 118+-3 mm Hg; P<.005). Nomega-Nitro-l-arginine methyl ester (L-NAME, 10 sup -7 to 10 sup -4 mol/L) evoked marked endothelium-dependent contractions in coronary arteries (young, 52+-8% of the contraction to 100 mmol/L KCl; adult, 40+-8%) but not aortas (young, 3+-1%; adult, 2+-1%). In coronary arteries, this response was significantly smaller in adult (n=9) than in young (n=8, P<.05) control rats. Young transgenic rats (56+-9%, n=8) showed slightly stronger contractions in response to L-NAME than young control rats (NS), which almost totally disappeared in adult transgenic rats (6+-3%, n=7; P<.05 versus adult control rats; P<.01 versus young transgenic rats). Endothelium-dependent relaxations in response to acetylcholine (10 sup -9 to 10 sup -4 mol/L) were totally blocked by L-NAME (10 sup -4 mol/L) but were unaffected by the thromboxane receptor antagonist SQ30741 (10 sup -7 mol/L). This stimulated release of EDNO, endothelium-independent relaxations in response to the nitrovasodilator linsidomine (10 sup -9 to 10 sup -5 mol/L), and contractions in response to KCl (100 mmol/L) were comparable in all groups of rats.Conclusions Ren-2 transgenic rats develop fulminant hypertension that is associated with a selective decrease in endothelium-dependent contractions in response to L-NAME, whereas endothelium-dependent relaxations in response to acetylcholine as well as smooth muscle function remain unaffected. (Circulation. 1994;89:2780-2786.)