摘要:

ObjectiveAngiotensin II (Ang II) increases insulin sensitivity in healthy volunteers. This effect is thought to be mediated, at least in part, by an increase in skeletal muscle blood flow. In the past it had been documented that some biological actions of Ang II are altered in diabetes. We addressed the issue of whether this is also true for its action on insulin sensitivity.Design and methodsTwelve healthy volunteers (aged 43 ± 9 years) and 15 patients with type 2 diabetes mellitus (NIDDM) of recent onset (aged 45 ± 9 years) were allocated in random order in a double-blind placebo-controlled design to be administered a sham infusion or an infusion of 2 ng Ang II/kg per min. Insulin-stimulated glucose uptake (the M value) was measured with the euglycaemic clamp technique, leg muscle blood flow (MBF) with plethysmography, blood pressure with a Dinamap device, and glomerular filtration rate and effective renal plasma flow with the steady-state inulin (Cin) andp-aminohippurate (CPAH) clearance methods, respectively.ResultsIn volunteers the mean M-value after Ang II infusion (10.1 ± 1.5 mg/kg per min) was significantly higher (P< 0.01) than that after sham infusion (8.2 ± 0.9 mg/kg per min). In contrast, in diabetic patients it was not significantly different with Ang II (6.1 ± 1.3 mg/kg per min) and sham infusion (5.5 ± 1.2 mg/kg per min). The difference in the mean absolute increase in the M value (ΔM) between groups was significant (P< 0.02). The Ang II-induced increase in MBF under euglycaemic conditions was attenuated in diabetic patients (from 15.0 ± 3.5 to 15.5 ± 3.9 ml/100 ml per min, NS) compared with volunteers (from 16.8 ± 3.3 to 19.1 ± 3.7 ml/100 ml per min,P< 0.01). Again, the difference between the mean absolute increases in MBF (ΔMBF) in the groups was significant (P< 0.01). A significant correlation was found between ΔMBF and ΔM (r = 0.62,P< 0.01). The absolute acute increase in mean arterial blood pressure with Ang II was similar in diabetic patients and volunteers. Mean Cin, CPAHand fractional sodium excretion values were significantly lower and renal vascular resistances and filtration fractions higher during the Ang II than they were during the placebo clamp period. This was observed in patients as well as in healthy subjects, but the effects of Ang II on renal haemodynamics and sodium handling were more pronounced in diabetic patients.ConclusionsIn patients with NIDDM of recent onset the stimulatory effect of Ang II on insulin sensitivity and on skeletal muscle blood flow is attenuated. In contrast, the effects of Ang II on renal perfusion and sodium handling are more pronounced in patients with NIDDM than they are in healthy subjects.

ISSN:0263-6352    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

BackgroundBehavioral stress has been proposed to contribute to the occurrence of myocardial ischemia.ObjectiveTo investigate the effect of chronic exposure to behavioral stress on the function and structure of the coronary artery of borderline hypertensive rats (BHR).DesignBHR were either exposed to an air-jet stress for 2 h/day for 10 days or kept in their cage for 10 days.MethodsAfter 10 days, hemodynamic measurements in conscious animals were recorded, and their hearts were removed for isolation of a left ventricular coronary artery for functional studies or for fixation by retrograde perfusion for study with scanning electron microscopy. Vascular reactivity was measured in isolated coronary arteries (≈250 μm) maintained at an intraluminal diameter of 40 mmHg while the intraluminal diameter was recorded continuously.ResultsThe resting mean arterial pressure and heart rate in conscious, unrestrained BHR were not altered significantly by exposure to 10 days of 2 h/day air-jet stress. Coronary artery relaxation in response to the endothelium-dependent vasodilator acetylcholine was impaired in rats exposed to the air-jet stress compared with that in controls. An attenuated response to exogenous nitric oxide in coronary arteries from stressed BHR was confirmed by the finding of a reduced sensitivity to nitroprusside, which releases nitric oxide independently from the endothelium. However, relaxation of coronary arteries in response to isoproterenol, which acts independently from nitric oxide, was not altered. Coronary artery contraction in response to endothelin-1 and phenylephrine was not altered in vessels taken from BHR exposed to behavioral stress compared with that in vessels from control rats. Scanning electron microscopy of the endothelial surface of the septal coronary artery showed no difference between vessels from control and stressed BHR.ConclusionThese results indicate that behavioral stress impairs endothelium-dependent and nitric oxide-mediated coronary relaxation, but does not alter α1-adrenoceptor or endothelin-1-mediated contraction. By impairing coronary artery vascular relaxation, chronic exposure to behavioral stress may contribute to myocardial ischemia.

ISSN:0263-6352    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

ObjectiveTo test the hypothesis that a reduction in left ventricular mass by long-term antihypertensive treatment, possibly associated with an improvement of diastolic function, would increase exercise performance in patients with essential hypertension.DesignAfter a placebo run-in period, 27 patients with essential hypertension World Health Organization stages I and II were assigned randomly to 6-month double-blind treatment with either a diuretic (hydrochlorothiazide plus triamterene) or a converting enzyme inhibitor (trandolapril), to which the calcium antagonist amlodipine could be added after 3 months if required for better blood pressure control.MethodsInvestigations included clinic and ambulatory blood pressure measurements, left ventricular imaging and transmitral Doppler echocardiography and graded maximal exercise testing on the bicycle ergometer with respiratory gas analysis.ResultsSix-month antihypertensive therapy, which caused significant (P< 0.001) reductions in blood pressure (by 16% for clinic pressure) and in left ventricular mass (by 13%), but without convincing evidence of improved diastolic function, did not affect exercise performance or peak oxygen uptake. The influence on clinic, exercise and ambulatory blood pressures and on the peak oxygen uptake was similar in the two treatment arms but left ventricular wall thickness decreased to a greater extent in the trandolapril group (P< 0.05 at 3 months andP= 0.06 at 6 months).ConclusionsRegression of left ventricular mass caused by 6-month antihypertensive therapy does not improve exercise performance of patients with essential hypertension.

ISSN:0263-6352    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

ObjectiveTo investigate the effect of cyclosporine A (CsA; Sandimmun Neoral) on systemic and renal hemodynamics, tubular function, and sodium excretion in healthy volunteers. Furthermore, we studied whether CsA enhances the systemic and renal hemodynamic sensitivity to norepinephrine.MethodsEighteen healthy volunteers were administered 10 mg/kg CsA or placebo capsules in a double-blind fashion. The mean arterial blood pressure (MAP), renal vascular resistance (RVR), glomerular filtration rate (GFR), and renal clearances of lithium (CLi) and sodium (CNa) were measured for 8 h after ingestion of the capsules. Norepinephrine (2 μg/kg per h) was infused intravenously for 1.5 h into nine subjects.ResultsCsA increased the MAP by 17 ± 2 mmHg. The GFR decreased by 18 ± 2% (P<0.001) and the RVR increased by 37 ± 4% (P< 0.001) after ingestion of CsA. The CsA-induced increase in MAP preceded the CsA-induced fall in GFR. The rise in MAP was followed by an early 35 ± 8% increase in CNa(P< 0.001). At the end of the 8 h study period, CNadecreased by 25 ± 7% (P< 0.001). Using CLi, it was found that the initial natriuresis had been caused by a relative decrease both in proximal and in distal tubular reabsorption of sodium, whereas the late sodium retention was secondary to the CsA-induced fall in GFR. Infusion of norepinephrine increased the MAP, RVR, and filtration fraction, and decreased the renal plasma flow, without CsA having any additional effect.ConclusionIt was demonstrated that a single oral dose of CsA caused a rise in blood pressure and transient natriuresis, followed by a fall in GFR and antinatriuresis. Thus, the present study confirms and extends earlier observations that renal dysfunction and sodium retention are not the initiating events in CsA-induced hypertension. The study also affords evidence suggesting that such rises in blood pressure are not mediated by an increased sensitivity to norepinephrine.

ISSN:0263-6352    

出版商:OVID    

年代:1997

数据来源: OVID