Monoclonal gammopathy with significance: case series and literature review.

Monoclonal gammopathy of undetermined significance (MGUS) is considered an asymptomatic precursor of malignant lymphoid disorders. This case series and literature review shows that these monoclonal gammopathies can cause significant morbidity. We describe a patient with angioedema due to acquired C1-esterase inhibitor deficiency, a patient with cryoglobulinemia type II causing skin vasculitis and glomerulonephritis, and a patient with glomerulonephritis and nephrotic syndrome - all caused by a monoclonal gammopathy that can be classified as MGUS. Clinicians should be familiar with these consequences of monoclonal gammopathies. The term MGUS should only be used in patients without organ damage caused by monoclonal gammopathies.

Dutch guideline for the management of hypertensive crisis -- 2010 revision.

Hypertensive crises are divided into hypertensive urgencies and emergencies. Together they form a heterogeneous group of acute hypertensive disorders depending on the presence or type of target organs involved. Despite better treatment options for hypertension, hypertensive crisis and its associated complications remain relatively common. In the Netherlands the number of patients starting renal replacement therapy because of 'malignant hypertension' has increased in the past two decades. In 2003, the first Dutch guideline on hypertensive crisis was released to allow a standardised evidence-based approach for patients presenting with a hypertensive crisis. In this paper we give an overview of the current management of hypertensive crisis and discuss several important changes incorporated in the 2010 revision. These changes include a modification in terminology replacing 'malignant hypertension' with 'hypertensive crisis with retinopathy and reclassification of hypertensive crisis with retinopathy under hypertensive emergencies instead of urgencies. With regard to the treatment of hypertensive emergencies, nicardipine instead of nitroprusside or labetalol is favoured for the management of perioperative hypertension, whereas labetalol has become the drug of choice for the treatment of hypertension associated with pre-eclampsia. For the treatment of hypertensive urgencies, oral administration of nifedipine retard instead of captopril is recommended as first-line therapy. In addition, a section on the management of hypertensive emergencies according to the type of target organ involved has been added. Efforts to increase the awareness and treatment of hypertension in the population at large may lower the incidence of hypertensive crisis and its complications.

Influence of atherosclerosis on age-related changes in renal size and function.

BACKGROUND: Renal size and function reflect the health of the kidney. These parameters are associated with age, gender and body weight. The kidneys are also influenced by micro- and macrovascular diseases. Atherosclerotic markers and risk factors may influence the age-related changes of renal size and function. METHODS: Data of 1056 patients who entered the SMART-study (Second Manifestations of ARTerial disease) were used to assess the effect of atherosclerosis on the relationship between age and renal size and function and to study the effect of atherosclerosis on renal size and function. Patients who were newly referred to the hospital with manifestations of vascular disease were screened for asymptomatic atherosclerosis with noninvasive tests. The carotid intima-media thickness (IMT) and albuminuria were used as estimates for the atherosclerotic burden. Renal size was defined as the mean pole-to-pole length of both kidneys measured by ultrasonography. Renal function was represented by serum creatinine. RESULTS: Intima-media thickness was a significant effect modifier of the age-renal size relationship (P = 0.041). The increase of serum creatinine with age was more pronounced in the highest tertile of IMT (P = 0.048). Renal size decreased equally with age in patients with and without hypertension or diabetes mellitus (DM). The same held true for the age-renal function relationship. Albuminuria and DM were independent predictors of renal size and function. CONCLUSION: Atherosclerosis accelerates the decrease of renal size and the increase of serum creatinine with age. Renal size and function are determined by albuminuria and DM.

The benefit of STent placement and blood pressure and lipid-lowering for the prevention of progression of renal dysfunction caused by Atherosclerotic ostial stenosis of the Renal artery. The STAR-study: rationale and study design.

BACKGROUND: Atherosclerotic renal artery stenosis (ARAS) is associated with progressive loss of renal function and is one of the most important causes of renal failure in the elderly. Current treatment includes restoration of the renal arterial lumen by endovascular stent placement. However, this treatment only affects damage caused by ARAS due to the stenosis and ensuing post-stenotic ischemia. ARAS patients have severe general vascular disease. Atherosclerosis and hypertension can also damage the kidney parenchyma causing renal failure. Medical treatment focuses on the latter. Lipid-lowering drugs (statins) could reduce renal failure progression and could reduce the overall high cardiovascular risk. The additional effect on preserving renal function of stent placement as compared to medical therapy alone is unknown. Therefore, the STAR-study aims to compare the effects of renal artery stent placement together with medication vs. medication alone on renal function in ARAS patients. METHOD: Patients with an ARAS of > or = 50% and renal failure (creatinine (Cr) clearance < 80 mL/min/1.73 m2) are randomly assigned to stent placement with medication or to medication alone. Medication consists of statins, anti-hypertensive drugs and antiplatelet therapy. Patients are followed for 2 yrs with extended follow-up to 5 yrs. The primary outcome of this study is a reduction in Cr clearance > 20% compared to baseline. This trial will include 140 patients.

Captopril renography and the relevance of abnormal but bilateral identical curves in the diagnosis of renal artery stenosis.

BACKGROUND: Captopril renography (CR) has been shown to improve the effectiveness of renal scintigraphy in renovascular hypertension, by inhibiting angiotensin-converting enzyme. CR is particularly sensitive and specific in unilateral renal artery stenosis (RAS), but results in patients with bilateral RAS are less favourable. The aim of this study was to investigate the meaning of abnormal but identical renographic curves in the diagnosis of RAS. PATIENTS AND METHODS: One hundred and fifty-eight patients clinically suspected for renovascular hypertension underwent CR, using 50 MBq (99)Tc(m)-mercaptoacetyltriglycine ((99)Tc(m)-MAG(3)), prior to performing renal angiography. CR was performed 1 h after captopril administration. Renograms were analysed according to the consensus criteria. All patients underwent angiography, considered as the "gold standard" in the detection of the presence of RAS (stenosis >50% was defined as significant). All kidneys were categorized into three groups, scintigraphically as well as angiographically: no stenosis, unilateral stenosis and bilateral stenosis. RESULTS: Out of 158 patients 100 (63%) showed a RAS on angiography (58 (37%) unilateral, 42 (26%) bilateral). The sensitivity and specificity of CR evaluated by patient was 83% and 75%, respectively. Thirty patients with completely identical curves were identified, 21 patients with normal curves and nine patients with abnormal identical curves. All but one patient showed no RAS on the angiogram. In this single patient a unilateral stenosis was found. CONCLUSION: Identical curves on the renogram generally suggest no RAS and are probably due to intrinsic parenchymal disease.

Plasma levels of cellular fibronectin in diabetes.

OBJECTIVE: Cellular fibronectin is an endothelium-derived protein involved in subendothelial matrix assembly. Elevated plasma levels of cellular fibronectin therefore reflect loss of endothelial cell polarization or injury to blood vessels. Consequently, elevated plasma levels of circulating cellular fibronectin have been described in clinical syndromes with vascular damage, although not in diabetes or atherosclerosis. RESEARCH DESIGN AND METHODS: We determined fibronectin levels in 52 patients with type 1 diabetes, 50 patients with type 2 diabetes, 54 patients with a history of ischemic stroke, 23 patients with renal artery stenosis, and 64 healthy subjects. RESULTS: Circulating cellular fibronectin was significantly elevated in patients with diabetes (4.3 +/- 2.8 microg/ml) compared with patients with ischemic stroke (2.0 +/- 0.9 microg/ml), patients with renovascular hypertension (1.7 +/- 1.1 microg/ml), and healthy subjects (1.4 +/- 0.6 microg/ml). Patients with diabetes and at least one cardiovascular risk factor had an almost 2.5-fold increase in cellular fibronectin compared with diabetic subjects without such a risk factor. In multivariate regression analysis, higher triglycerides, current or past cigarette smoking, and higher urinary albumin excretion were independently associated with an increase in circulating cellular fibronectin in diabetes. CONCLUSIONS: These results suggest that circulating cellular fibronectin may be a marker protein for endothelial cell activation, especially in diabetes. Prospective studies are needed to explore this possibility

Aspirin renography and captopril renography in the diagnosis of renal artery stenosis.

UNLABELLED: Preliminary data suggest that aspirin renography is more sensitive than captopril renography for indicating renal artery stenosis (RAS). Considering that aspirin, compared with captopril, reduces renal blood flow and, thus, tubular tracer delivery in poststenotic kidneys, aspirin renography is expected to be more useful, particularly if tubular tracers are used. METHODS: We prospectively compared aspirin renography (20 mg/kg orally) and captopril renography (25 mg orally) with 99mTc-mercaptoacetyltriglycine in 75 consecutive patients suspected of having RAS. RESULTS: RAS, diagnosed as stenosis of more than 50% on angiography, was found unilaterally in 34 patients and bilaterally in 17 patients. RAS was absent in 24 patients. The sensitivities for unilateral RAS or bilateral RAS (i.e., stenosis that was at least unilateral) were, respectively, 88% and 88% for captopril renography and 82% and 94% for aspirin renography (not significant). The overall specificity was 75% for captopril renography and 83% for aspirin renography (not significant). Tracer uptake ratios, time to peak activity, and percentage of 20-min tracer retention were also not significantly different for captopril and aspirin renography. Subgroup analysis of modest (50-75%) and severe (> or =75%) RAS, or of plasma creatinine greater than 120 micromol/L, also showed no difference between captopril and aspirin renography. CONCLUSION: We conclude that for identification of RAS, the usefulness of aspirin renography equals, but does not surpass, that of captopril renography.

Assessment of renal artery stenosis: comparison of captopril renography and gadolinium-enhanced breath-hold MR angiography.

AIM: To determine the accuracy of captopril renography (CR) and gadolinium-enhanced breath-hold magnetic resonance (MR) angiography in the diagnosis of 50-99% renal artery stenosis (RAS). MATERIALS AND METHODS: Forty-three patients with possible RAS, of whom 53% had renal function impairment (creatinine >130 micromol/l), were included.(99m)Tc-mercaptoacetyl triglycine (MAG(3)) renography was performed after an oral dose of 25 mg captopril. Gadolinium-enhanced MR angiography was performed on a standard 1.5 Tesla system: TR 13.5, TE 3.5, flip angle 60 degrees, matrix 195 x 512. Intra-arterial digital subtraction angiography (DSA) was the standard of reference. RESULTS: Captropril renography accurately categorized 22 of 26 patients who had either uni- or bilateral RAS of 50-99%. The sensitivity and specificity of CR for the detection of 50-99% stenosis were 85 and 71%, respectively. With MR angiography one occluded artery was incorrectly diagnosed as a stenosis. Sensitivity and specificity were 100 and 94%, respectively. The difference between the accuracies of MR angiography and CR was statistically significant (P = 0.02). The accuracy of CR was lower in patients with renal impairment (70%) than in those with normal renal function (90%). CONCLUSION: MR angiography showed a high accuracy in diagnosing RAS of between 50 and 99%. CR was less accurate than MR angiography, especially in patients with renal function impairment. In patients with normal renal function, however, CR remains a useful diagnostic test.

Duplex ultrasonography in assessing restenosis of renal artery stents.

PURPOSE: To determine the accuracy and optimal threshold values of duplex ultrasonography (US) in assessing restenosis of renal artery stents. METHODS: Twenty-four consecutive patients with 33 renal arteries that had previously been treated with placement of a Palmaz stent underwent duplex US prior to intraarterial digital subtraction angiography (DSA), which was the reference standard. Diagnostic accuracy of in-stent peak systolic velocity (PSV) and reno-aortic ratio (RAR = PSV renal stent/PSV aorta) in detecting > 50% in-stent restenosis were evaluated by the receiver operating characteristic curve. Sensitivity and specificity were determined using the optimal threshold values, and using published threshold values: RAR > 3.5 and in-stent PSV > 180 cm/sec. RESULTS: Six examinations were technically inadequate. Nine stents had residual or restenosis > 50% at DSA. The two duplex parameters were equally accurate since areas under the curves were similar (0.943). With optimal threshold values of 226 cm/sec for PSV and 2.7 for RAR, sensitivities and specificities were 100% and 90%, and 100% and 84%, respectively. Using the published duplex criteria resulted in sensitivities and specificities of 100% and 74% for PSV, and 50% and 89% for RAR. CONCLUSION: Duplex US is a sensitive modality for detecting in-stent restenosis if laboratory-specific threshold values are used.

Renal volume measurements: accuracy and repeatability of US compared with that of MR imaging.

PURPOSE: To determine the accuracy and repeatability of ultrasonography (US) with the ellipsoid formula in calculating the renal volume. MATERIALS AND METHODS: The renal volumes in 20 volunteers aged 19-51 years were determined by using US with the ellipsoid formula and magnetic resonance (MR) imaging with the voxel-count method by two independent observers for each modality. The observers performed all measurements twice, with an interval between the first and second examinations. The voxel-count method was the reference standard. Repeatability was evaluated by calculating the SD of the difference (method of Bland and Altman). RESULTS: Renal volume was underestimated with US by 45 mL (25%) on average. A comparable underestimation was found when the ellipsoid formula was applied to MR images. This indicates that the inaccuracy of US renal volume measurements (a) occurred because the kidney does not resemble an ellipsoid and (b) was not primarily related to the imaging modality. Intra- and interobserver variations in US volume measurements were poor; the SD of the difference was 21-32 mL. For comparison, the SD of the difference in reference-standard measurements was 5-10 mL. CONCLUSION: Use of US with the ellipsoid formula is not appropriate for accurate and reproducible calculation of renal volume.

Arterial stenting and balloon angioplasty in ostial atherosclerotic renovascular disease: a randomised trial.

BACKGROUND: Percutaneous transluminal angioplasty (PTA) for ostial atherosclerotic renal-artery stenosis has poor results. Angioplasty with stent placement (PTAS) may be more effective. We undertook a randomised prospective study to compare PTA with PTAS in patients with ostial atherosclerotic renal-artery stenosis. METHODS: Patients with ostial atherosclerotic renal-artery stenosis were assigned to receive PTA or PTAS. Secondary PTAS was allowed if PTA failed immediately or during 6 months' follow-up. Analysis was by intention to treat. FINDINGS: 42 patients were assigned PTA and 43 were assigned PTAS, but one patient in the PTAS group was excluded from the study. Primary success rate (<50% residual stenosis) of PTA was 57% (24 patients) compared with 88% (37 patients) for PTAS (difference between groups 31% [95% CI 12-50]). Complications were similar. At 6 months, the primary patency rate was 29% (12 patients) for PTA, and 75% (30 patients) for PTAS (46% [24-68]). Restenosis after a successful primary procedure occurred in 48% of patients for PTA and 14% for PTAS (34% [11-58]). 12 patients underwent secondary stenting for primary or late failure of PTA within the follow-up period: success was similar to that of primary PTAS. Evaluation based on intention to treat showed no difference in clinical results at six months for PTA or PTAS. INTERPRETATION: PTAS is a better technique than PTA to achieve vessel patency in ostial atherosclerotic renal-artery stenosis. Primary PTAS and primary PTA plus PTAS as rescue therapy have similar outcomes. However, the burden of reintervention after PTA outweighs the potential saving in stents, so primary PTAS is a better approach to use.

[Treatment of renal artery stenosis with intra-arterial stents]. / Behandeling van nierarteriestenosen met intra-arteriële stents.

In some patients with hypertension or renal insufficiency, renal artery stenosis can play a causative part. If fibromuscular dysplasia is the pathology of the stenosis, treatment of the stenosis by transluminal percutaneous renal angioplasty (TPRA) results in improvement of the concomitant hypertension in 80-90% of the patients. In case of atherosclerotic lesions 50% of the patients benefit by such treatment. In renal insufficiency TPRA of atherosclerotic lesions results in improvement of renal function in only one third of the patients. As restenosis and elastic recoil are seen as the prime determinants of this lack of success in atherosclerosis, intravascular stents were developed with the aim to accomplish a permanent dilation of the arterial lumen. In recent studies stent placement resulted in cure of high blood pressure in 0-16% of the patients and in improvement in 35-70%. The percentage of improvement must be viewed with caution because of the open design of these studies. Improvement of renal function was reported in 7-36% of the patients and worsening in 8-18%. Based on these outcomes stent placement in stenosed renal arteries should not be regarded as a routine clinical treatment.

Spiral CT angiography of the renal arteries: should a scan delay based on a test bolus injection or a fixed scan delay be used to obtain maximum enhancement of the vessels?

PURPOSE: The purpose of this work was to assess the optimal scan delay for spiral CT angiography (SCTA) of the renal arteries in achieving optimal vascular contrast enhancement and to compare the utility of a delay based on these bolus injection versus that of a fixed scan delay. METHOD: Seventy patients underwent renal artery SCTA with a 140 ml bolus of contrast agent injected a 3 ml/s. In 35 patients (Group A), a fixed scan delay of 27 s was used; in the other 35 (Group B), the scan delay was based on the transit time (TTest) of a test bolus injection. The scan delays in this group were set at TTest + 5 s (n = 5), TTest + 10 s (n = 8), TTest + 15 s (n = 4), or TTest + 20 s (n = 18). For all 70 patients, the time intervals between TRA (time to scanning the renal arteries) and TMax (time to maximum aortic enhancement after 140 ml bolus injection) were calculated, after which it was determined in which group of patients TRA occurred closest to TMax. Linear regression and mean squared error (MSE) were used for statistical analysis. RESULTS: For Group A, mean TRA and TMax were 38 and 50 s, respectively. Mean (TRA - TMax) was -12 s with MSE of 185.76. For Group B, mean TRA and Tmax were 45 and 52 s. Mean (TRA - TMax) values were -15, -12, -11, and -1 s for scan delays of TTEST + 5 s, TTEST + 10 s, TTest + 15 s, and TTEST + 20 s, respectively, with MSEs of 253.80, 158.00, 137.50, and 30.00. CONCLUSION: SCTA of the renal arteries was best performed with a scan delay of TTEST + 20 s. However, analysis of our data showed that similar results could be expected with a delay of 44 s.

Renal artery stenosis and accessory renal arteries: accuracy of detection and visualization with gadolinium-enhanced breath-hold MR angiography.

PURPOSE: To determine the accuracy of gadolinium-enhanced breath-hold magnetic resonance (MR) angiography in the diagnosis of renal artery stenosis and visualization of accessory renal arteries. MATERIALS AND METHODS: Forty-four patients suspected of having renal artery stenosis and 10 potential kidney donors, all of whom were scheduled to undergo elective intraarterial digital subtraction angiography (DSA), were studied. Three-dimensional gradient-echo gadolinium-enhanced MR angiography was performed at 1.5 T with the following parameters: repetition time, 13.5 msec; echo time, 3.5 msec; flip angle, 60 degrees; 195 x 512 matrix; 400-mm field of view; and 6-cm imaging volume consisting of 15 4-mm-thick partitions reconstructed every 2 mm. Gadopentetate dimeglumine (30 mL) was injected with a power injector. MR angiograms were assessed before the standard of reference, intraarterial DSA, was performed. RESULTS: Four MR angiograms were not evaluable because of poor image quality. MR angiography enabled visualization of all but one of the 121 arteries. In four small accessory arteries, a stenosis could not be excluded owing to inadequate spatial resolution. MR angiography enabled the correct diagnosis in 30 of the 31 arteries with a grade 2 (50%-99%) stenosis and in seven of the 10 occluded arteries. Sensitivity and specificity for correct identification of a grade 2 stenosis were 97% and 92%, respectively. CONCLUSION: Gadolinium-enhanced MR angiography is an accurate, minimally invasive method for detecting renal artery stenosis and is reliable for visualizing accessory renal arteries.

Angiotensin converting enzyme inhibitor-induced renal dysfunction in atherosclerotic renovascular disease.

Ischemic nephropathy due to bilateral renovascular disease (RVD) is increasingly recognized as cause of end-stage renal failure in the elderly, but a reliable non-invasive method of detection is nor available. Angiotensin converting enzyme inhibition (ACEi) may impair renal function in such patients, but a prospective study of its diagnostic validity has not been undertaken. We studied the effects of controlled exposure to ACEi on plasma creatinine in 108 patients at risk for severe bilateral atherosclerotic RVD, and compared the findings with subsequent angiography. ACEi was given for two weeks, or, to avoid acute renal failure, for four days if plasma creatinine had increased by 20% or more. If after two weeks of ACEi plasma creatinine had not increased by > or = 20%, while blood pressure was still elevated, plasma creatinine was remeasured after blood pressure control by addition of diuretics. The severity of RVD was scored by the stenosis grade of the best perfused kidney. Fifty-two patients had severe bilateral RVD, defined as > or = 50% stenosis to both kidneys (N = 23) or a solitary functioning kidney (N = 29). Of the others, 21 had less severe bilateral RVD, 20 unilateral RVD, and 15 no apparent RVD. Basal plasma creatinine was higher in severe bilateral RVD (median 170 mumol/liter, range 85 to 654 mumol/liter) than in the others (122 mumol/liter, 62 to 675 mumol/liter; P < 0.01), but not discriminative due to a large variability. The increase during ACEi was correlated with the degree of RVD (r = 0.53, P < 0.001). In 69 patients ACEi caused at least a 20% increase in plasma creatinine, in 26 cases by four days, in 31 after two weeks, and in 12 only after blood pressure control by diuretics. Among these were all 52 patients with severe bilateral RVD, 15 of the 41 patients with lesser forms of RVD, and two with normal renal arteries. Thus, in this selected population the criterion of > or = 20% rise in plasma creatinine upon ACEi was 100% sensitive to detect severe bilateral RVD, while its specificity was 70%. No case of acute renal failure was encountered, and plasma creatinine always recovered after stopping ACEi. In conclusion, controlled exposure to ACEi in these patients is safe, and ACEi-induced increase in plasma creatinine is a very sensitive detector of severe bilateral RVD in a high risk population.

Progressive vascular damage in hypertension is associated with increased levels of circulating P-selectin.

OBJECTIVE: To assess whether increased shedding of adhesion molecules in plasma provides an index for endothelial damage in hypertension. DESIGN AND METHODS: Three groups of hypertensive patients with increasing severity of vascular damage were studied: 20 essential hypertensives, 21 atherosclerotic, renovascular hypertensives and four malignant hypertensives. Twenty healthy subjects were included as a control group. Levels of P-selectin, E-selectin, intracellular adhesion molecule 1, vascular cell adhesion molecule and von Willebrand factor in venous blood were measured, using sandwich-type enzyme-linked immunosorbent assay. RESULTS: For essential hypertensives a trend for increased P-selectin and E-selectin values compared with those in controls was observed (159+/-44 versus 132+/-40 ng/ml, P = 0.062 and 40+/-13 versus 34+/-17 ng/ml, P = 0.055, respectively). P-selectin (210+/-84 ng/ml, P = 0.0021) and E-selectin (42+/-12 ng/ml, P = 0.012) levels in renovascular hypertensives were significantly higher than those in healthy controls. There were no significant increases in circulating levels of intracellular adhesion molecule 1, vascular cell adhesion molecule and von Willebrand factor either in essential hypertensives or in renovascular hypertensives. Marked increases in circulating levels of adhesion molecules and von Willebrand factor relative to those in controls were observed in malignant hypertensives (P-selectin 634+/-332 versus 132+/-40 ng/ml, P = 0.0004; vascular cell adhesion molecule 968+/-187 versus 493+/-139 ng/ml, P = 0.0004; and von Willebrand factor 259+/-75 versus 130+/-72 U/dl, P = 0.016). CONCLUSIONS: Progression of vascular damage in essential, renovascular and malignant hypertension is associated with a rise in circulating levels of P-selectins and, to a lesser extent, E-selectins, whereas levels of intracellular adhesion molecule 1, vascular cell adhesion molecule and von Willebrand factor are elevated only in diseases associated with acute severe vascular damage, including malignant hypertension. Our data suggest that selectins may be useful as indicators of vascular damage in hypertension.

Divergent effects of ACE-inhibition and calcium channel blockade on NO-activity in systemic and renal circulation in essential hypertension.

OBJECTIVE: Nitric oxide is a vasodilating and blood pressure lowering substance. To investigate whether calcium antagonists or angiotensin-converting enzyme (ACE) inhibitors increase vascular nitric oxide activity, we assessed systemic and renal vascular sensitivity to nitric oxide synthase inhibition in hypertensives on and off medication. METHODS: Ten essential hypertensive patients, aged 22-51 years, were studied 3 times: > or = 4 weeks off medication, after 3 weeks treatment with enalapril 20 mg twice a day and after 3 weeks nifedipine 60 mg/day. Each time, 24-h blood pressure registration was performed, followed by a clearance study to obtain a 3-h dose-response curve for intravenously infused NG-monomethyl-L-arginine (L-NMMA, respectively 0.75, 1.5 and 3.0 mg/kg/h). RESULTS: L-NMMA dose-dependently increased mean arterial pressure with 5 +/- 2 mmHg and systemic vascular resistance with 24 +/- 5% at maximum dose, whereas cardiac output decreased (all P < 0.001). Enalapril and nifedipine treatment decreased blood pressure, while the L-NMMA-induced increase in systemic vascular resistance was potentiated (enalapril: 45 +/- 7% and nifedipine: 46 +/- 8%; both P < 0.01). L-NMMA also dose-dependently decreased renal blood flow by 58 +/- 8% at maximum dose (P < 0.001), but neither drug potentiated these effects. CONCLUSION: These results indicate that, in essential hypertensives, antihypertensive therapy with enalapril or nifedipine increases nitric oxide dependency of systemic vascular tone, which may play a role in the blood pressure lowering effect of these drugs. However, this phenomenon cannot be observed in the renal circulation, suggesting a different regulation of endothelium-dependent vasomotion in the hypertensive kidney.