A randomized, double-blind study of valsartan versus metoprolol on arterial distensibility and endothelial function in essential hypertension.

BACKGROUND: Antihypertensive drugs may have differential, pressure-independent effects on hypertension-associated alterations of arterial function. We compared the effects of a 12-week therapy with the AT(1)-receptor antagonist valsartan (Val) versus the beta-blocker metoprolol (Met) on arterial stiffness and endothelial function in mildly hypertensive patients at rest and during generalized sympathetic stimulation. METHODS: Sixty-eight patients (37 male, 31 female, 46 +/- 6 years) were randomized to Val (80-160 mg/d) or Met (50-100 mg/d). Effects of therapy on endothelial function, brachial and carotid artery distensibility coefficients, pulse wave velocity, carotid intima-media thickness and elastic modulus were assessed at rest and during the cold pressor test. RESULTS: Fifty-two patients were available for per protocol analysis. Blood pressure was comparably reduced in both treatment groups. Effects on endothelial function and large artery elastic wall properties did not differ significantly between the two antihypertensive treatment regimens. Trends did not differ significantly between groups for any parameter including carotid intima-media thickness and elastic modulus. CONCLUSION: Short-term treatment with Val and Met had similar effects on large artery functional vessel wall properties in a population of mildly hypertensive patients.

Sympathetic nerve activity in renal transplant patients before and after withdrawal of cyclosporine.

BACKGROUND: It has been suggested that the increase in blood pressure observed in transplant patients treated with cyclosporine is mediated by cyclosporine-induced sympathoexcitation. However, the chronic effects of cyclosporine on sympathetic outflow in renal transplant patients have not been investigated. Therefore we studied sympathetic nerve activity and blood pressure before and 6 months after the withdrawal of cyclosporine in renal transplant patients. METHODS: Twenty-four renal transplant patients with histologically confirmed chronic allograft nephropathy (age 48 +/- 3 years, 60 +/- 10 months after transplantation) were included in the prospective study and randomly assigned to either withdrawal (n = 12) or continuation (n = 12) of cyclosporine. Both groups received mycophenolate mofetil and prednisolone as additional immunosuppressants. At entry and 6 months later blood pressure, muscle sympathetic nerve activity (MSNA), and plasma norepinephrine were measured. To assess the potential influence of the diseased native kidneys, three renal transplant patients who had their native kidneys removed were studied before and after cyclosporine withdrawal. RESULTS: Mean arterial pressure decreased significantly in the cyclosporine-withdrawal group (95 +/- 4 versus 105 +/- 4 mmHg 6 versus 0 months, P < 0.05) but not in the cyclosporine-continuation group (103 +/- 3 versus 105 +/- 4 mmHg, NS). However, plasma norepinephrine and MSNA did not change significantly in either group (MSNA 43 +/- 4 versus 44 +/- 3 and 38 +/- 5 versus 39 +/- 4 bursts/min in the cyclosporine-withdrawal and cyclosporine-continuation groups, NS). Graft function remained stable in both groups and in transplant patients who had their native kidneys removed MSNA did not decrease after cyclosporine withdrawal. CONCLUSION: The withdrawal of cyclosporine in renal transplant patients, receiving relatively low doses of cyclosporine, resulted in a substantial decrease in blood pressure. However, MSNA and norepinephrine did not change. This suggests that cyclosporine treatment does not cause chronic sympathetic activation that could explain the cyclosporine-induced blood pressure elevation in renal transplant patients.

Dialysis filter type determines the acute effect of haemodialysis on endothelial function and oxidative stress.

BACKGROUND: Endothelial function of large arteries is impaired in chronic haemodialysis patients and oxidative stress due to the dialysis procedure has been suggested as a causal factor. However, it is not clear whether different types of dialysis membranes affect endothelial function differently. Therefore we determined endothelium-dependent, flow-mediated dilatation (FMD) of the brachial artery as well as markers of oxidative stress immediately before and after haemodialysis (HD) with either a cellulosic cuprophane or a synthetic polysulphone dialyser in a blinded, randomized, cross-over study. METHODS: Twelve haemodialysis patients (age 55+/-3 years, time on dialysis 20+/-2 months, mean fluid change -1782+/-21 ml, systolic/diastolic blood pressure 139/75 mmHg) were included. Using a multi-gate-pulsed Doppler system (echo-tracking device) brachial artery FMD and nitroglycerine-induced, endothelium-independent vasodilatation (NMD) were measured. Patients were randomized to HD with either a polysulphone or a cuprophane membrane and were crossed over to the other filter. Investigators were blinded to the type of membrane used. Serum concentrations of oxidized LDL (oxLDL) and alpha-tocopherol as markers of oxidative stress were measured before and after each dialysis session. RESULTS: Data are given as mean+/-SEM. Treatment with polysulphone filter HD did not significantly affect FMD (baseline 9.3+/-2.0% vs after HD 9.6+/-1.8%). After dialysis with a cuprophane membrane FMD decreased from 9.4+/-2.1 to 7.4+/-1.8% (P<0.05). NMD was not significantly affected by HD irrespective of the membrane material used. Serum levels of oxLDL were not changed by either treatment; however, alpha-tocopherol concentrations fell significantly after dialysis with the cuprophane filter (baseline 18.0+/-2.3 after HD 16.6+/-1.3 micro g/ml, P<0.05), while alpha-tocopherol levels remained unchanged when the polysulphone membrane was used. CONCLUSIONS: The type of dialysis filter membrane determines the acute effect of haemodialysis on arterial endothelial function. Differences in biocompatibility and oxidative stress may account for the observed differential effects, since the decrease of FMD after dialysis with a cellulosic cuprophane membrane-but not with a synthetic polysulphone membrane-was associated with a reduction in serum vitamin E.