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Biomedical subjects

H A Koomans

Publications and source records attributed to H A Koomans.

At least 19 recordsLinked to original sources
PubMed2002

[Gene-expression analysis using DNA microarrays].

Parallel to the efforts to unravel the human genome code, techniques are currently being developed to analyse the activity of all genes and proteins in a cell population or tissue. The most advanced of these functional genomic techniques is that used to study gene expression using DNA microarrays, also known as 'DNA chips'. This allows the expression of thousands of different genes to be compared in two different samples (for example, one from a sick person and one from a healthy one). Bioinformatics is essential in this technique. The expression profiles obtained in this way can be used to characterise complex biological situations (e.g., cell division and apoptosis) and diseases. There have already been reports on the opportunities in the diagnostic work-up for leukaemias and breast cancer. There are also applications on the more basic level, such as discovering precisely how the transcription apparatus works, and finding new genes and identifying their role. The use of microarrays in medicine is still in its infancy. It is anticipated that this and similar genome-wide analysis techniques will help in the elucidation of pathophysiological mechanisms, in making diagnoses and prognoses, and in monitoring treatment. The justifiable enthusiasm should, however, be accompanied by quality control, international standardisation and a critical approach towards the interpretation of results.

Diagnostic Techniques and Procedures↗
PubMed2001

Mechanisms and consequences of arterial hypertension after renal transplantation.

The high incidence of hypertension after renal transplantation contributes to the risk of cardiovascular morbidity and mortality in renal transplant recipients. Although cyclosporine has been influential in the improvement of transplant outcome, it has emerged as a major cause of hypertension after organ transplantation. The underlying pathophysiological mechanisms of cyclosporine-induced hypertension include enhanced sympathetic nervous system activity, renal vasoconstriction, and sodium/water retention. Hypertension is also significantly associated with reduced graft survival and thereby requires aggressive treatment intervention. Calcium channel blockers may offer some advantages over angiotensin-converting enzyme inhibitors for the treatment of hypertension in stable renal transplant recipients. Nevertheless, selection of the most appropriate antihypertensive agent should take into account the possibility of pharmacokinetic interactions with immunosuppressive agents. There is evidence to suggest that the use of tacrolimus-based immunosuppression induces less hypertension compared with cyclosporine. Not only do patients receiving tacrolimus tend to require less antihypertensive therapy, but converting patients from cyclosporine to tacrolimus has been shown to result in significant reductions in blood pressure. Thus, tacrolimus may be associated with an improved cardiovascular risk profile in renal transplant recipients.

Antihypertensive Agents↗
PubMed2001

Predisposition of spontaneously hypertensive rats to develop renal injury during nitric oxide synthase inhibition.

Chronic nitric oxide (NO) synthase (NOS) inhibition results in renal injury. Hypertension is an important risk factor for renal injury. We studied the influence of preexistent hypertension on the sensitivity for renal injury induced by chronic NOS inhibition in rats. Spontaneously hypertensive (SHR) and normotensive Wistar-Kyoto (WKY) rats were treated with 3, 10, 30 and 100 mg/l Nomega-nitro-L-arginine (L-NNA) until death. Systolic blood pressure and proteinuria were measured regularly and compared with time-control measurements in untreated SHR and WKY. In WKY, 3 and 10 mg/l L-NNA did not affect systolic blood pressure, while 30 and 100 mg/l L-NNA resulted in an increase in systolic blood pressure after 12 and 4 weeks, respectively. In contrast in SHR, every dose of L-NNA resulted in an increase in systolic blood pressure after 2 weeks. In WKY, 3 and 10 mg/l L-NNA did not affect proteinuria or survival, while 30 and 100 mg/l L-NNA resulted in an increase in proteinuria after 30 and 9 weeks, and a median survival of 36 and 12 weeks, respectively. In SHR, 3, 10, 30 and 100 mg/l L-NNA resulted in an increase in proteinuria after 30, 12, 3 and 3 weeks, and a median survival of 41, 20, 5 and 3 weeks, respectively. Thus, at every dose of the inhibitor, chronic NOS inhibition resulted in far earlier increases in systolic blood pressure and proteinuria and a marked increase in mortality in SHR as compared to WKY. Indeed, a very low dosage of L-NNA that caused no harm in WKY was followed by marked increases in proteinuria and blood pressure and decreased survival in SHR. Hypertension strongly increases the vulnerability to cardiovascular risk factors that compromise the NO-system.

Animals↗
PubMed2001

Losartan versus enalapril on cerebral edema and proteinuria in stroke-prone hypertensive rats.

Stroke-prone spontaneously hypertensive rats (SHRSP), subjected to high NaCl, show severe hypertension, organ damage, and early death. Preventive treatment with angiotensin II type 1 (AT1) receptor antagonists is known to be effective. Previously, we found that angiotensin converting enzyme (ACE) inhibition could reduce cerebral edema when treatment was started after manifestation of either proteinuria or cerebral edema. In this study AT1 receptor blockade was started at the same time points to evaluate whether this had an effect superior to ACE inhibition. SHRSP drank 1% NaCl. Group 1 served as controls. Group 2 and 3 rats were started on losartan and enalapril after proteinuria exceeded 40 mg/day. Group 4 and 5 rats were started on losartan and enalapril after the first observation of cerebral edema with T2-weighted magnetic resonance imaging scans. In controls, median survival was 54 days (range, 35 to 80 days) after the start of salt loading. With early-onset losartan and enalapril, survival increased to 305 days (range, 184 to 422 days) and 320 days (range, 134 to 368 days) (both P < .01 v group 1). Cerebral edema formation was prevented in all but two rats, one from each treatment modality. Development of proteinuria was markedly reduced. With late-onset treatment with losartan and enalapril, survival was 290 days (range, 120 to 367 days) and 264 days (range, 154 to 319 days) (both P < .01). Both losartan and enalapril decreased cerebral edema to baseline levels. Ultimately cerebral edema reoccurred, despite continued treatment, in 75% of the rats. Systolic blood pressure did not decrease after losartan treatment, but, similarly to early-onset treatment, decreased transiently after enalapril treatment. Cerebral edema and proteinuria were prevented and reduced in SHRSP treated with either an AT1 receptor antagonist or an ACE inhibitor. Survival was markedly and similarly prolonged by both treatments, whether initiated directly before or after development of cerebral edema. In rats where treatment was initiated after manifestation of cerebral edema, both cerebral edema and proteinuria reappeared despite continued treatment. Apparently, when hypertension is sustained, reappearance of target organ damage may not be entirely dependent on angiotensin.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed2001

Graft surveillance: venous pressure, access flow, or the combination?

BACKGROUND: Increased venous pressure (VP) and decreased access flow (Qa) are predictors of dialysis access graft thrombosis. VP is easily obtainable. Qa assessment requires a special device and takes more time. The aims of our randomized multicenter studies were to compare outcome in patients with grafts monitored by VP or Qa (study A) or monitored by VP or the combination of VP and Qa (study B). METHODS: We performed VP measurements consisting of weekly VP at a pump flow of 200 mL/min (VP200) and the ratio of VP0/MAP. Qa was measured every eight weeks with the Transonic HD01 hemodialysis monitor. Threshold levels for referral for angiography were VP200> 150 mm Hg or VP0/MAP> 0.5 (both at 3 consecutive dialysis sessions) or Qa <600 mL/min. Subsequent therapy consisted of either percutaneous transluminal angioplasty (PTA) or surgery. RESULTS: Total follow-up was 80.5 patient-years for 125 grafts. The vast majority of a total of 131 positive tests was followed by angiography and corrective intervention. In study A, the rate of thromboses not preceded by a positive test was 0.19 and 0.24 per patient-year (P = NS), and in study B, it was 0.32 versus 0.28 per patient-year (P = NS). Survival curves were not significantly different between the subgroups. CONCLUSIONS: These data demonstrate that standardized monitoring of either VP or Qa or the combination of both and subsequent corrective intervention can reduce thrombosis rate in grafts to below the recommended quality of care standard (that is, 0.5 per patient-year, NKF-DOQI). These surveillance strategies are equally effective in reducing thrombosis rates.

Adult↗
PubMed2001

Albumin restores lysophosphatidylcholine-induced inhibition of vasodilation in rat aorta.

BACKGROUND: Impairment of vasodilation by oxidized low-density lipoprotein has been attributed to lysophosphatidylcholine (LPC). Albumin avidly binds LPC. Therefore, hypoalbuminemia may directly impair vasodilation and thus contribute to increased risk of atherosclerosis in nephrotic syndrome. The addition of albumin reduces LPC in erythrocytes and endothelial cells. We hypothesized that the addition of albumin will salvage vasodilation in aortic rings previously exposed to LPC. LPC increases superoxide production and disturbs L-arginine availability. Therefore, we also decreased superoxide with a superoxide dismutase mimic, MnCl(2), and supplemented L-arginine in an attempt to restore vasodilation. METHODS: Rat aorta rings, which had been incubated with various concentrations of LPC and human serum albumin (HSA), were mounted in organ chambers. Relaxation was studied with acetylcholine (0.01 to 100 micromol/L) after precontraction with phenylephrine (CON, 0.3 micromol/L; LPC, 0.03 micromol/L). In some studies MnCl(2) or L-arginine was added to the organ chamber. RESULTS: LPC had time- and dose-dependent inhibitory effects on acetylcholine-mediated vasodilation, but no effect on nitroprusside-mediated vasodilation. Preincubation with albumin (50 or 6 g/L) could protect vasodilation against very high levels of LPC. After preincubation with LPC, the addition of albumin to the incubation salvaged vasodilation. Albumin was more effective after short LPC incubation. MnCl(2) had no specific effect on the LPC-mediated disturbance in vasodilation. L-arginine completely salvaged vasodilation at low concentrations of LPC. However, even high concentrations of L-arginine (1 mmol/L) could not improve vasodilation at LPC levels at which vasodilation was restored by albumin. CONCLUSIONS: LPC affects several pathways that inhibit vasodilation, all of which are salvaged by addition of albumin.

Acetylcholine↗
PubMed2000

Unchanged cardiac angiotensin II levels accompany losartan-sensitive cardiac injury due to nitric oxide synthase inhibition.

Chronic nitric oxide synthase (NOS) inhibition results in hypertension and myocardial injury. In a rapid and severe model of chronic NOS inhibition, we determined the role of angiotensin II in these effects by using angiotensin II receptor blockade and by measuring cardiac angiotensin II concentrations before and during development of cardiac damage. Rats received either no treatment, the NOS inhibitor Nomega-nitro-L-arginine (L-NNA; 500 mg/l), the angiotensin AT(1) receptor antagonist losartan (400 mg/kg chow), or L-NNA plus losartan for 21 days. In the second protocol, five groups of rats received L-NNA (500 mg/l) for 0, 4, 7, 14 and 21 days, respectively. L-NNA increased systolic blood pressure (SBP) (227+/-8 versus 143+/-6 mm Hg; P<0.01), heart weight index (0.44+/-0.02 versus 0.32+/-0.01; P<0.01) and induced coronary vasculitis and myocardial necrosis. Co-treatment with losartan prevented all changes. L-NNA during 4 days decreased cardiac angiotensin II (23+/-4 versus 61+/-15 fmol/g; P<0.05). Although after 7 days, fresh infarcts and after 14 days organized infarcts were present, cardiac angiotensin II was only slightly increased after 21 days (100+/-10 fmol/g; P<0.05). In conclusion, losartan-sensitive cardiac damage due to chronic NOS inhibition is not associated with primary increase of cardiac angiotensin II, suggesting that chronic NOS inhibition increases cardiac sensitivity for angiotensin II.

Angiotensin II↗
PubMed2000

Conversion to mycophenolate mofetil in conjunction with stepwise withdrawal of cyclosporine in stable renal transplant recipients.

BACKGROUND: Mycophenolate mofetil (MMF) is now part of standard immunosuppression in the first phase after renal transplantation. A relevant question is if it can replace drugs such as cyclosporine (CsA) in the maintenance treatment, improving cardiovascular risk profile. METHODS: In 17 patients with a stable renal function (at least 6 months) posttransplantation, we studied the effect of CsA replacement by MMF. After starting MMF (1 g b.i.d.), CsA dosage was reduced from regular to low (median trough level 130 microg/L, respectively, 45 microg/L), followed by complete withdrawal, while prednisone (7.5 mg daily) was continued. We measured ambulatory blood pressure, glomerular filtration rate, renal plasma flow, renal vascular resistance, and metabolic factors at start and after 8 weeks on regular, low-dose CsA, respectively, no CsA with MMF and prednisone. RESULTS: Two patients dropped out after the switch to low-dose CsA/MMF, due to diarrhea in one and a steroid responsive rejection in the other. The complete switch from CsA to MMF was successful in all 15 patients and accompanied by a decrease in 24 hr systolic blood pressure (from 152+/-13 to 145+/-13 mmHg; P<0.01), diastolic blood pressure (93+/-9 to 89+/-12 mmHg; P<0.05), RVR (0.29+/-0.06 to 0.25+/-0.09 mmHg.ml/min; P<0.05), and an increase in glomerular filtration rate (46.6+/-8.8 to 58.0+/-10.5 ml/min; P<0.01) and renal plasma flow. Intermediate low density lipoprotein-cholesterol decreased (0.79+/-0.37 to 0.41+/-0.16 mmol/L; P<0.01). High density lipoprotein-cholesterol decreased, but remained in the safe range. After 1 year two patients stopped the MMF; one because of Kaposi's sarcoma and one because of recurrent infections CONCLUSIONS: The stepwise switch from CsA to MMF was safe and mostly successful, and had beneficial effects on blood pressure, glomerular hemodynamics, and lipid profile. Beneficial trends were already present after partial withdrawal of CsA.

Adult↗
PubMed2000

ACE inhibition delays development of terminal renal failure in the presence of severe albuminuria.

The hypertensive fawn-hooded (FHH) rat develops progressive albuminuria (UalbV) and focal glomerulosclerosis (FGS). Early-onset angiotensin-converting enzyme inhibition (ACE-i) completely prevented the development of hypertension, UalbV, and FGS. ACE-i was still effective when the start of treatment was delayed, albeit less than early-onset treatment. In this study, we examined whether more advanced renal damage reduces the efficacy of ACE-i, and, if so, which factors dampen the efficacy. ACE-i was started in 36-week-old FHH rats, and follow-up consisted of regular assessment of systolic blood pressure (SBP) and UalbV. Untreated rats, matched for age, SBP, and UalbV, served as controls. In separate groups, untreated or treated with ACE-i from either week 7 or week 36, glomerular hemodynamics and FGS were determined at week 40. ACE-i normalized SBP and markedly reduced UalbV. The Initial UalbV response to ACE-i was inversely correlated with pretreatment UalbV, but despite control of SBP, UalbV rose again. Eventually, rats died of terminal renal failure. Life expectancy was significantly increased in treated rats. In both untreated and treated rats, there was a significant inverse correlation between baseline UalbV and survival time. However, the gain in survival time decreased when pretreatment UalbV was higher. Late-onset ACE-i reduced glomerular capillary pressure to the same extent as early-onset ACE-i. There was a significant linear correlation between FGS and UalbV. We conclude that in FHH rats with advanced renal damage, ACE-i slows down the progression to terminal renal failure. The outcome is an increased survival time that is inversely correlated with baseline UalbV.

Albuminuria↗
PubMed2000

Concerted actions of renal endothelial and macula densa NO systems in the maintenance of extracellular fluid volume.

It is now clear that nitric oxide (NO) exerts a substantial influence on renal function and that the kidney has a high capacity to produce NO. However, there are at least two different NO systems in the kidney. The interplay between NO generated by the endothelium and by the macula densa is considered in this review. It seems that endothelial NO increases in response to an increase in perfusion pressure and an increase in distal delivery, whereas macula densa NO decreases upon a sustained increase in distal delivery. Furthermore, evidence is accumulating that macula densa NO may well mediate renin release. Though seemingly in contrast, both the response of the endothelial NO and of the macula densa NO system seem appropriate to restore a perturbation of fluid balance. The function of the tubuloglomerular feedback (TGF) mechanism is likely to be influenced by both sources of NO, because of the close proximity of these NO producing cells to the vascular smooth muscle cells of the afferent arteriole. The endothelial NO system seems to be responsible for short-term, dampening actions to increased afferent arteriolar tone elicited by activation of the TGF system. The macula densa NO system, on the other hand, is probably adapting TGF responses to sustained increases in distal delivery. The analysis presented in this paper is an attempt to integrate the function of the two NO systems into physiological regulation. The exact role of the medullary NOS enzymes remains to be further elucidated.

Angiotensin II↗
PubMed2000

Male gender increases sensitivity to proteinuria induced by mild NOS inhibition in rats: role of sex hormones.

Men are at greater risk for renal injury than women. We studied whether male rats are more sensitive to the hypertensive and proteinuric effects of chronic nitric oxide synthase (NOS) inhibition than female rats. In addition, we studied whether androgens or estrogens are responsible for differences in sensitivity to proteinuria induced by chronic NOS inhibition. Females and males were treated with 10, 20, 30, and 100 mg/l N(omega)-nitro-L-arginine (L-NNA) during 24 wk. Systolic blood pressure (SBP) and proteinuria were measured regularly and compared with time-control measurements in control females and males. In females and males treatment with 10 mg/l L-NNA had no effect on SBP or proteinuria. Treatment with 20, 30, and 100 mg/l L-NNA resulted in a dose-dependent increase in SBP that was similar in males and females. However, females treated with 20 and 30 mg/l L-NNA were resistant to the development of proteinuria: maximum values were 16 +/- 7 and 46 +/- 21, respectively, vs. 16 +/- 3 mg/day in controls, whereas males treated with those doses showed an increase in proteinuria [139 +/- 35 (P < 0.05) and 318 +/- 82 (P < 0.01), respectively, vs. 55 +/- 11 mg/day in controls]. Treatment with 100 mg/l L-NNA increased proteinuria similarly in both females and males. To study the role of sex hormones in differences in sensitivity to proteinuria induced by mild chronic NOS inhibition, treatment with 20 mg/l L-NNA was repeated in ovariectomized (Ovx) and orchidectomized rats. Ovariectomy did not affect the increase in SBP caused by 20 mg/l L-NNA, but, in contrast to intact females, this dose of L-NNA did cause Ovx rats to develop proteinuria (51 +/- 16 vs. 16 +/- 7 mg/day in control Ovx rats; P < 0.05). Orchidectomy completely prevented the increased SBP as well as proteinuria induced by 20 mg/l L-NNA in male rats. In conclusion, male rats are more sensitive than female rats to develop proteinuria induced by mild chronic NOS inhibition. Estrogens provide some protection in females, whereas androgens are responsible for the increased sensitivity of male rats to proteinuria induced by mild chronic NOS inhibition. Risk factors associated with a compromised nitric oxide system may be more detrimental to the kidney in men than in women.

Androgens↗
PubMed2000

Normal TGF responsiveness during chronic treatment with angiotensin-converting enzyme inhibition: role of AT1 receptors.

Acute inhibition of angiotensin II formation by angiotensin-converting enzyme inhibition (ACE-I) attenuates tubuloglomerular feedback (TGF) responsiveness. This has been proposed to facilitate sodium excretion, which contributes to the antihypertensive effects of ACE-I. However, in previous experiments in spontaneously hypertensive Fawn-hooded rats, TGF responses were normal during chronic ACE-I treatment. In the present study, we investigated TGF responsiveness during chronic ACE-I treatment in normotensive rats and the involvement of changes in nitric oxide or angiotensin II activity. Maximum TGF responses were assessed in control Sprague-Dawley rats and in rats acutely (acute ACE-I, 3 microgram/min IV) and chronically (chronic ACE-I, 100 mg/L PO 2 to 3 weeks+acute 3 microgram/min enalaprilat IV) treated with ACE-I. In all groups, TGF responses were also assessed during late proximal tubular perfusion with 1 mmol/L nitro-L-arginine. In a last group, the chronic ACE-I treatment was combined with acute ACE-I and high doses of intrarenal losartan (acute 3 microgram/min enalaprilat IV+50 mg/kg losartan). The maximum TGF responses in acutely treated ACE-I rats were strongly attenuated (0.7+/-0.4 mm Hg versus 6.5+/-0.8 mm Hg in control rats, P<0.05). Mean arterial pressure was lower in the chronically treated ACE-I group (107+/-5 mm Hg versus 126+/-5 mm Hg in control rats, P<0.05); however, TGF responses were normal (6. 4+/-0.9 mm Hg). Intraluminal nitro-L-arginine infusion did not influence TGF responses during acute ACE-I (2.3+/-0.4 mm Hg) but enhanced TGF responses during chronic ACE-I to the same extent as in control rats (14.5+/-2.3 versus 16.7+/-1.9 mm Hg, NS). In the rats chronically treated with ACE-I with superimposed acute infusion of losartan or chronically treated with losartan, TGF responses were significantly attenuated (1.8+/-0.8 mm Hg and 2.6+/-0.8 mm Hg, respectively; P:<0.05 versus chronic ACE-I and control). Prolonged administration with ACE-I is associated with normal TGF responses. This phenomenon appears to be mediated by AT1 receptors, because acute treatment with losartan in rats chronically treated with ACE-I and chronic treatment with losartan lead to strong attenuation of TGF responses.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed2000

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.

Aged↗
PubMed1999

Effects of oral folic acid supplementation on endothelial function in familial hypercholesterolemia. A randomized placebo-controlled trial.

BACKGROUND: Folates have been suggested to be of benefit in reducing cardiovascular risk. The present study was designed to examine whether oral folic acid supplementation could improve endothelial function as an intermediate end point for cardiovascular risk in patients with increased risk of atherosclerosis due to familial hypercholesterolemia (FH). METHODS AND RESULTS: In a prospective, randomized, double-blind, placebo-controlled study with crossover design, we evaluated the effects of 4 weeks of treatment with oral folic acid (5 mg PO) on endothelial function in FH. In 20 FH patients, forearm vascular function was assessed at baseline, after 4 weeks of folic acid treatment, and after 4 weeks of placebo treatment by venous occlusion plethysmography, with serotonin and sodium nitroprusside used as endothelium-dependent and -independent vasodilators. In addition, we examined the vasoconstrictor response to the NO synthase inhibitor N(G)-monomethyl-L-arginine to assess basal NO activity. In FH patients, folic acid supplementation restored the impaired endothelium-dependent vasodilation, whereas it did not significantly influence endothelium-independent vasodilation or basal forearm vasomotion. There was a trend toward improvement in basal NO activity. CONCLUSIONS: These data demonstrate that oral supplementation of folic acid can improve endothelial function in patients with increased risk of atherosclerotic disease due to hypercholesterolemia, without changes in plasma lipids.

Administration, Oral↗
PubMed1999

Reduction of sympathetic hyperactivity by enalapril in patients with chronic renal failure.

BACKGROUND: Inhibition of angiotensin-converting enzyme (ACE) reduces the risk of cardiovascular problems in patients with chronic renal failure. This effect may be due in part to a decrease in sympathetic nervous activity, but no direct evidence of such an action is available. METHODS: We studied muscle sympathetic-nerve activity in 14 patients with hypertension, chronic renal failure, and increased plasma renin activity before, during, and after administration of the ACE inhibitor enalapril. Ten other patients with similar clinical characteristics were studied before and during treatment with the calcium-channel blocker amlodipine. Normal subjects matched for age and weight were included in both studies. RESULTS: At base line, mean (+/-SD) muscle sympathetic-nerve activity was higher in the group of patients who received enalapril than in the control subjects (35+/-17 vs. 19+/-9 bursts per minute, P=0.004). The baroreflex curve, which reflects changes in muscle sympathetic-nerve activity caused by manipulations of blood pressure with sodium nitroprusside and phenylephrine, was shifted to the right in the patients, but baroreflex sensitivity was similar to that in the control subjects (-2.1+/-1.9 and -2.7+/-1.3 bursts per minute per mm Hg, respectively; P=0.36). A single dose of the sympatholytic drug clonidine caused a greater fall in blood pressure in the patients than in the control subjects. Treatment with enalapril normalized blood pressure and muscle sympathetic-nerve activity (at 23+/-10 bursts per minute) in the patients and shifted the baroreflex curve to the left, reflecting normal blood-pressure levels, without significantly changing sensitivity (-2.3+/-1.8 bursts per minute per mm Hg, P=0.96). In the patients who received amlodipine, treatment also lowered blood pressure but increased muscle sympathetic-nerve activity, from 41+/-19 to 56+/-14 bursts per minute (P=0.02). CONCLUSIONS: Increased sympathetic activity contributes to hypertension in patients with chronic renal disease. ACE inhibition controls hypertension and decreases sympathetic hyperactivity.

Amlodipine↗