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(...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.展开更多
Hypothesis test on the population mean with various inequality constraints is studied in this paper.The empirical likelihood method is applied to construct test statistics.Limiting distributions of the empirical likel...Hypothesis test on the population mean with various inequality constraints is studied in this paper.The empirical likelihood method is applied to construct test statistics.Limiting distributions of the empirical likelihood ratio test statistics are proven to be a weighted mixture of chi-square distributions.Numerical results are presented to show the validity of the proposed method.展开更多
文摘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.
基金supported by National Nature Science Foundation of China(Grant No.10731010),National Nature Science Fund for Creative Research Groups(GrantNo.10721101)Key Fund of Yunnan Province(Grant No.2010CC003)
文摘Hypothesis test on the population mean with various inequality constraints is studied in this paper.The empirical likelihood method is applied to construct test statistics.Limiting distributions of the empirical likelihood ratio test statistics are proven to be a weighted mixture of chi-square distributions.Numerical results are presented to show the validity of the proposed method.
