Background: Acute inhibition of nitric oxide synthase results in systemic and renal vasoconstriction, which might be attributable to unopposed activity of the sympathetic nervous(SNS) and the renin-angiotensin system(RAS). We studied the effects of NG-nitro-L-arginine methyl ester(L-NAME)during α1-adrenoceptor blockade and concomitant angiotensin II type 1(AT1)receptor blockade in hypertensive individuals pretreated with hydrochlorothiazide(Hct; 25 mg once daily). Methods: Thirteen individuals(47±9 years) were studied during administration of placebo, and after pretreatment with Hct +doxazosin(Dox; 8 mg twice daily for 9 days), with Hct+Dox+losartan(Los; 50 mg twice daily for 9 days), or(n=5) with doxazosin or Dox+Los without hydrochlorothiazide. Mean arterial pressure(MAP) and cardiac output were derived from the finger blood pressure signal recorded by Finapres. Systemic vascular resistance(SVR) was calculated as MAP/cardiac output. Five renal clearance studies of 40 min were performed. Renal vascular resistance(RVR) was calculated as MAP divided by renal blood flow(RBF). L-NAME(12.5 μg/kg per min intravenously) was given during the third clearance period. Results: MAP was 113±11 mmHg at baseline and decreased to 99±10 mmHg during the administration of Hct+Dox and to 92±10 mmHg during Hct+Dox+Los. This decrease in MAP was caused by a decrease in SVR(P=0.0009). Pretreatment with Hct+Dox or Hct+Dox+Los had no effect on glomerular filtration rate or RBF. Infusion of L-NAME during the administration of Hct+Dox resulted in an augmented(P< 0.0001) increase in MAP(18%), SVR(61%)and RVR(70%) compared with those observed with placebo(8, 30 and 49%, respectively). This augmentation was abolished by losartan. Conclusion: L-NAME-in-duced systemic and renal vasoconstrictor responses are potentiated during α1-adrenoceptor blockade. This potentiation was abolished by AT1-receptor antagonism. In man, unopposed activity of the SNS or SNS and RAS is not involved in the systemic and renal vasoconstriction induced by L-NAME. Background: Acute inhibition of nitric oxide synthase results in systemic and renal vasoconstriction, which might be attributable to unopposed activity of the sympathetic nervous (SNS) and the renin-angiotensin system (RAS). We studied the effects of NG-nitro-L- arginine methyl ester (L-NAME) during α1-adrenoceptor blockade and concomitant angiotensin II type 1 (AT1) receptor blockade in hypertensive individuals pretreated with hydrochlorothiazide (Hct; 25 mg once daily). Methods: Thirteen individuals studied during administration of placebo, and after pretreatment with Hct + doxazosin (Dox; 8 mg twice daily for 9 days) with Hct + Dox + losartan (Los; 50 mg twice daily for 9 days), or (n = 5) with Mean arterial pressure (MAP) and cardiac output were derived from the finger blood pressure signal recorded by Finapres. Systemic vascular resistance (SVR) was calculated as MAP / cardiac output. Five renal clearance studies of 40 min were perfo Renal vascular resistance (RVR) was calculated as MAP divided by renal blood flow (RBF). L-NAME (12.5 μg / kg per min intravenously) was given during the third clearance period. Results: MAP was 113 ± 11 mmHg at baseline and decreased to 99 ± 10 mmHg during the administration of Hct + Dox and to 92 ± 10 mmHg during Hct + Dox + Los. This decrease in MAP was caused by a decrease in SVR (P = 0.0009). Pretreatment with Hct + Dox or Hct + Dox + Los had no effect on glomerular filtration rate or RBF. Infusion of L-NAME during the administration of Hct + Dox resulted in an augmented (P <0.0001) increase in MAP (18%), SVR and Augmented RVR (70%) compared with those observed with placebo (8, 30 and 49%, respectively). This augmentation was abolished by losartan. Conclusion: L-NAME-in-duced systemic and renal vasoconstrictor responses are potentiated during α1-adrenoceptor blockade. This potentiation was abolished by AT1-receptor antagonism. In man, unopposed activity of the SNS or SNS and RAS is not involved in the syste mic andrenal vasoconstriction induced by L-NAME.