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Biomedical subjects

A H van den Meiracker

Publications and source records attributed to A H van den Meiracker.

At least 19 recordsLinked to original sources
PubMed2003

[Primary hyperaldosteronism].

Primary hyperaldosteronism (PHA), autonomic secretion of aldosterone by the adrenal gland, is rare. PHA usually results in therapy-resistant hypertension and is often but not always accompanied by hypokalaemia. Common causes of PHA are an aldosterone-producing adenoma, idiopathic aldosterone hypersecretion, unilateral hyperplasia or a genetic variant: glucocorticoid-remediable aldosteronism (GRA). The diagnosis should be phased and first of all requires a biochemical confirmation of the presence of PHA. In PHA patients, plasma renin is invariably suppressed. Blood should be collected under standardised conditions while the patient is not using beta-blockers or centrally-acting antihypertensive medication. Patients with a suppressed plasma renin and an elevated plasma aldosterone concentration have PHA. In patients with a suppressed plasma renin and a high-normal plasma aldosterone concentration a confirming test should be performed in which PHA is diagnosed if aldosterone is not suppressed following volume expansion with sodium chloride. The cause of PHA is determined by means of a CT scan or MRI of the adrenal glands to find a unilateral adenoma. If the CT scan or MRI is normal, adrenal vein aldosterone sampling may be considered as a next step in order to demonstrate lateralisation of aldosterone production. The hypertension and hypokalaemia of all forms of PHA respond well to spironolactone therapy. In the case of a unilateral adenoma or unilateral hyperplasia, adrenalectomy is the treatment of choice. For GRA, dexamethasone in doses that reduce the corticotropin (ACTH) level is indicated.

Adenoma↗
PubMed2003

[Atrial and B-type natriuretic peptides: from the research lab to clinical practice].

The heart produces two related hormones, atrial (ANP) and B-type natriuretic peptides (BNP). Both are synthesized in the atria and ventricles as polypeptides, which upon release are split into ANP and BNP and the N-terminal fragments N-ANP and N-BNP (together named natriuretic peptides, NPs). The most important function of ANP and BNP is protection against volume-overload, by increasing natriuresis and diuresis amongst other things. Both peptides can be considered the natural antagonist of the renin-angiotensin system. Clearance occurs through a specific receptor and through enzymatic break-down by neutral endopeptidase (NEP). All 4 NPs circulate in plasma. Elevated concentrations of NPs are found when the filling pressures of the heart are elevated, as in acute coronary syndromes and congestive heart failure. Measurement of NPs is a useful tool in the differential diagnosis of cardiac versus non-cardiac dyspnoe (high negative predictive value), in the identification of heart failure patients most at risk and in optimising therapy in heart failure. In right ventricular overload caused by (corrected) congenital heart diseases and acute lung embolism, NP concentrations are also elevated, as they are in renal failure and in hypertension associated with left ventricular hypertrophy. Infusions of ANP and BNP lead to increased natriuresis and diuresis. Pharmacologically, increases in ANP and BNP can be accomplished with NEP-inhibitors or beta-blockers. Measurement of NP(s) will become as important for estimation of heart function as creatinine is for estimation of renal function.

Atrial Natriuretic Factor↗
PubMed2003

Comparison between serum creatinine and creatinine clearance for the prediction of postoperative mortality in patients undergoing major vascular surgery.

BACKGROUND: Poor renal function prior to surgery is associated with increased risk for mortality in patients undergoing major vascular surgery. Traditionally, this function is assessed by serum creatinine concentration (SeCreat). However, SeCreat is also influenced by age, gender and body weight. Hence, creatinine clearance (C(Cr)) is considered to be a better reflection of renal function. This study was undertaken to explore the prognostic value of preoperative calculated Cc, compared to SeCreat for the prediction of postoperative mortality. PATIENTS AND METHODS: The study group comprised 852 consecutive patients who underwent elective major vascular surgery at the Erasmus Medical Center, Rotterdam. Preoperative C(Cr) was calculated based on the Cockroft-Gault equation using preoperative SeCreat, age, body weight and gender. Univariable logistic regression analyses were used to study the relation between preoperative SeCreat, C(Cr) and postoperative mortality. Furthermore, multivariable logistic regression analysis was applied to evaluate the additional predictive value of age, body weight and gender additional to SeCreat. The receiver operating characteristic (ROC) curve was determined to evaluate the predictive power of several regression models for perioperative mortality. RESULTS: Postoperative mortality was 5.9% (50/852) within 30 days of surgery. In a univariable analysis, 10 micromol/l increment of SeCreat were associated with a 20% increased risk of postoperative mortality (OR = 1.2, 95% CI, 1.1-1.3) with an area under the ROC curve of 0.64 (95% CI, 0.56-0.71). If age, gender and body weight were added, the area under the ROC curve increased to 0.70 (95% CI, 0.63-0.77; p < 0.001), indicating that these risk factors had additional prognostic value. Indeed, in a separate regression analysis 10 ml/min decrease in C(Cr) was associated with a 40% increased risk of postoperative mortality (OR = 1.4,95% CI, 1.2-1.5; ROC area: 0.70, 95% CI, 0.63-0.76). ROC curve analysis showed that the cut-off value of 64 ml/min for C(Cr) yielded the highest sensitivity/specificity to predict postoperative mortality. CONCLUSION: Preoperative SeCreat was strongly associated with postoperative mortality, and adding age, gender, and body weight to the model showed improved predictive power indicating that preoperative C(Cr) calculated with these data has additional prognostic value.

Adult↗
PubMed2002

Spectral analysis of heart rate and blood pressure variability in primary Sjögren's syndrome.

BACKGROUND: Autonomic dysfunction has been described in primary Sjögren's syndrome (SS). OBJECTIVE: To investigate the circulatory autonomic regulation in patients with primary SS by power spectral analysis of heart rate and blood pressure variability. METHODS: Forty three (42 female) patients with primary SS, mean age 52 years (range 23-80), with a mean disease duration of eight years (range 1-30) and 30 (15 female) healthy controls, mean age 43 years (range 21-68) were studied. In each patient blood pressure, heart rate, and respiration were measured continuously during supine rest and orthostatic challenge (60 degrees head-up tilt). Power spectral analysis was performed to determine possible differences in short term sympathetic and parasympathetic autonomic regulation between patients and controls. Furthermore, spectral parameters were studied in relation to illness severity and disease duration of the patients with primary SS. RESULTS: After controlling for differences in age, heart rate variability of the mid-frequency band and the variation coefficient of systolic blood pressure were significantly lower in patients with primary SS than in controls during supine rest. During 60 degrees tilt patients with primary SS showed a significantly higher mean heart rate, mean systolic blood pressure, and variation coefficient of diastolic blood pressure, and a significantly lower baroreflex index than controls. After controlling for age, no differences were found either in heart rate variability, blood pressure results, and baroreflex sensitivity during supine rest and tilt between the subgroups divided according to disease duration, Schirmer test results, or between the subgroups with different fatigue scores. No differences were found in spectral data between the groups with and without positive antinuclear antibody serology. CONCLUSION: For the group no differences in sympathetic and parasympathetic cardiac control were seen between patients with primary SS and controls, as assessed by spectral techniques, although some cardiovascular differences were found, particularly during orthostatic challenge.

Adult↗
PubMed2002

The value of plasma markers for the clinical behaviour of phaeochromocytomas.

OBJECTIVE: Phaeochromocytomas (PCCs) are widely known for their clinical unpredictability. This study intends to define predictive plasma markers for their variable postoperative behaviour. Furthermore, the diagnostic accuracy of these plasma tests was determined. DESIGN AND METHODS: A retrospective correlative study was performed in a series of 83 operated and four autopsied patients in order to correlate preoperative catecholamine (CAT) levels of 103 PCCs with their clinical behaviour. In a subset of cases, chromogranin-A (Chr-A) and enzymes/precursors of the CAT biosynthesis were studied for their predictive value. RESULTS: Basal CAT levels were elevated in 81/87 instances (sensitivity: 93%). Four of six cases with normal measurements showed only medullary hyperplasia. Larger PCCs, particularly those showing necrosis, capsular and vascular invasion, secreted higher CAT levels. Bilateral, hereditary tumours were less productive than their unilateral counterparts. Extra-adrenal PCCs secreted significantly lower levels of epinephrine (EPI) than intra-adrenal tumours. Fourteen patients developed metastases. According to Kaplan-Meier estimations, patients with higher levels of dopamine, norepinephrine (NE) and aromatic l-amino acid decarboxylase as well as lower ratios of EPI/EPI+NE, had significantly shorter metastases-free intervals. Existence of preoperative hypertension, left ventricular hypertrophy and measured blood pressures showed significant positive relationships with CAT levels, but not with Chr-A. CONCLUSIONS: These data showed that plasma CAT measurement is a sensitive method in the diagnostic work-up of PCCs. Those tumours producing normal levels are commonly small and asymptomatic. Furthermore, certain secretion patterns are indicative of the presence of metastases as well as the size and site of sporadic and syndrome-related PCCs.

Adolescent↗
PubMed2001

Cardioprotection in pigs by exogenous norepinephrine but not by cerebral ischemia-induced release of endogenous norepinephrine.

BACKGROUND AND PURPOSE: Endogenous norepinephrine release induced by cerebral ischemia may lead to small areas of necrosis in normal hearts. Conversely, norepinephrine may be one of the mediators that limit myocardial infarct size by ischemic preconditioning. Because brief ischemia in kidneys or skeletal muscle limits infarct size produced by coronary artery occlusion, we investigated whether cardiac norepinephrine release during transient cerebral ischemia also elicits remote myocardial preconditioning. METHODS: Forty-one crossbred pigs of either sex were assigned to 1 of 7 experimental groups, of which in 6 groups myocardial infarct size was determined after a 60-minute coronary occlusion and 120 minutes of reperfusion. One group served as control (no pretreatment), while the other groups were pretreated with either cerebral ischemia or an intracoronary infusion of norepinephrine. RESULTS: In 10 anesthetized control pigs, infarct size was 84+/-3% (mean+/-SEM) of the area at risk after a 60-minute coronary occlusion and 120 minutes of reperfusion. Intracoronary infusion of 0.03 nmol/kg. min(-)(1) norepinephrine for 10 minutes before coronary occlusion did not affect infarct size (80+/-3%; n=6), whereas infusion of 0.12 nmol/kg. min(-)(1) limited infarct size (65+/-2%; n=7; P:<0.05). Neither 10-minute (n=5) nor 30-minute (n=6) cerebral ischemia produced by elevation of intracranial pressure before coronary occlusion affected infarct size (83+/-4% and 82+/-3%, respectively). Myocardial interstitial norepinephrine levels tripled during cerebral ischemia and during low-dose norepinephrine but increased 10-fold during high-dose norepinephrine. Norepinephrine levels increased progressively up to 500-fold in the area at risk during the 60-minute coronary occlusion, independent of the pretreatment, while norepinephrine levels remained unchanged in adjacent nonischemic myocardium and arterial plasma. CONCLUSIONS: Cerebral ischemia preceding a coronary occlusion did not modify infarct size, which is likely related to the modest increase in myocardial norepinephrine levels during cerebral ischemia. The infarct size limitation by high-dose exogenous norepinephrine is not associated with blunting of the ischemia-induced increase in myocardial interstitial norepinephrine levels.

Animals↗
PubMed2001

Involvement of the peripheral nervous system in primary Sjögren's syndrome.

BACKGROUND: Involvement of the peripheral nervous system in patients with primary Sjögren's syndrome (SS) has been reported, but its prevalence in neurologically asymptomatic patients is not well known. OBJECTIVE: To assess clinical and neurophysiological features of the peripheral nervous system in patients with primary SS. PATIENTS AND METHODS: 39 (38 female) consecutive patients with primary SS, aged 20-81 years (mean 50), with a disease duration of 1-30 years (mean 8) were studied. The peripheral nervous system was evaluated by a questionnaire, physical examination, quantified sensory neurological examination, and neurophysiological measurements (nerve conduction studies). To assess autonomic cardiovascular function an orthostatic challenge test, a Valsalva manoeuvre, a forced respiration test, and pupillography were done. RESULTS: Abnormalities as indicated in the questionnaire were found in 8/39 (21%) patients, while an abnormal neurological examination was found in 7/39 (18%) patients. Abnormalities in quantified sensory neurological examination were found in 22/38 (58%) patients. In 9/39 (23%) patients, neurophysiological signs compatible with a sensory polyneuropathy were found. No differences were found in the autonomic test results, disease duration, serological parameters, or erythrocyte sedimentation rate between the patients with primary SS with and those without evidence of peripheral nervous involvement. CONCLUSION: Subclinical abnormalities of the peripheral nervous system may occur in patients with primary SS selected from a department of rheumatology, but clinically relevant involvement of the peripheral nervous system in this patient group is rare.

Adult↗
PubMed2000

Variation in semicarbazide-sensitive amine oxidase activity in plasma and tissues of mammals.

Semicarbazide-sensitive amine oxidase (SSAO) (E.C. 1.4.3.6) is a group of enzymes with as yet poorly understood function which is widely present in nature. The variation in methodology for determination of activity, differences in substrates used and in nomenclature have made it difficult to compare SSAO in different species and tissues. Since SSAO is implicated in the pathophysiology of diabetes mellitus and congestive heart failure, our aim was to analyse the importance and abundance of SSAO in human plasma and tissues compared to other mammals. In plasma of ten different mammals, Vmax values were found to vary more than 10,000-fold, while KM differed much less; in human plasma SSAO activity is relatively low. In some species more than one SSAO entity was present in plasma. SSAO activity was ubiquitous in tissues of human, rat and pig, but varied considerably, both between species and between tissues. In human tissues, SSAO activity is higher than in tissues from rat and pig. Relative to monoamine oxidase-B there is also wide variation in SSAO, with much higher relative activities in human than in rat and pig tissues. We conclude that in plasma, SSAO activity is highest in ruminants, while in tissues, SSAO activity is more prominently present in human than in rat and pig.

Amine Oxidase (Copper-Containing)↗
PubMed2000

Plasma semicarbazide-sensitive amine oxidase (SSAO) is an independent prognostic marker for mortality in chronic heart failure.

AIMS: Experimental evidence has suggested that semicarbazide-sensitive amine oxidase is involved in vascular endothelial damage and in the process of atherosclerosis, through the formation of reactive aldehydes, hydrogen peroxide and ammonia from endogenous substrates. Recent evidence indicates that semicarbazide-sensitive amine oxidase may be identical with the vascular adhesion protein-1. In patients with diabetes mellitus and chronic heart failure the plasma activity is raised relative to the severity of the disease. The prognostic value of plasma semicarbazide-sensitive amine oxidase is not known. METHODS AND RESULTS: Plasma semicarbazide-sensitive amine oxidase activity was measured at baseline in patients with moderate to severe chronic heart failure who participated in a large European study (PRIME-II). The 372 patients who took part in a pre-defined substudy in The Netherlands were investigated and a survival follow-up (maximum 5.4 years, mean 3.4 years) was carried out. Within the follow-up period 195 patients died. Plasma semicarbazide-sensitive amine oxidase was higher at baseline in those who died than in the survivors (653+/-258 vs 540+/-242 mU. l(-1), P<0.001). Dividing the patients into two groups according to plasma values above or below the median value of 550 mU. l(-1), semicarbazide-sensitive amine oxidase was found to be a prognostic parameter for survival, both in univariate (P<0.0001) and in multivariate (P=0.0106) analysis. Semicarbazide-sensitive amine oxidase values >550 mU. l(-1)had a 1. 50 (95% CI, 1.10-2.04) times increased risk of death. CONCLUSION: The finding that plasma semicarbazide-sensitive amine oxidase is an independent prognostic marker for mortality in chronic heart failure supports the concept that an elevated plasma semicarbazide-sensitive amine oxidase level has deleterious effects, possibly due to vascular endothelial damage.

Aged↗
PubMed2000

Assessment of body position to quantify its effect on nocturnal blood pressure under ambulatory conditions.

BACKGROUND: Nocturnal blood pressure readings may be influenced by body position because of variation in the vertical distance between heart and cuff level. OBJECTIVES: To quantify the effect of body position on nocturnal blood pressure and to assess whether this effect influences the reproducibility of nocturnal blood pressure. PATIENTS AND METHODS: In 16 individuals (three normotensive and 13 hypertensive) 24 h ambulatory measurement of blood pressure and body position was performed twice, separated by an interval of 2-6 weeks. Body position was measured with five acceleration sensors, which were mounted on the trunk and legs. RESULTS: During the first night, 43 +/- 31% of blood pressure values were measured while participants were in the supine position, 29 +/- 28% when they were lying on their side with the cuffed arm down and 28 +/- 29% when they were lying on their side with the cuffed arm up. During the second night these percentages were 40 +/- 29%, 32 +/- 29% and 28 +/- 25% respectively. Blood pressure readings obtained while individuals were lying with the cuffed arm up were about 10 mmHg lower than those obtained with the individual in either the supine position or lying with the cuffed arm down. After correction for the underestimation attributable to 'cuff-up' readings, nocturnal blood pressure increased by 3 mmHg and the number of non-dippers increased from two to four. Correction did not affect the reproducibility of nocturnal blood pressure measurements (standard deviation of the differences 8.3 mmHg for systolic and 6.0 mmHg for diastolic blood pressure after correction). Dipping status was reproduced in 88% of individuals before correction, and in 87% after correction. CONCLUSIONS: Under ambulatory conditions, a highly variable but sometimes substantial number of blood pressure readings are taken with the cuffed arm above heart level. These readings result in underestimation of nocturnal blood pressure and hence influence dipper-non-dipper classification. However, body position does not seem to have an important influence on the reproducibility of nocturnal blood pressure or dipping status.

Adult↗
PubMed1999

[Hypertensive crisis: definition, pathophysiology and treatment].

Hypertensive crises are currently subdivided into hypertensive emergencies and urgencies depending on the acuteness with which the elevated blood pressure has to be lowered. Malignant hypertension, defined as severe hypertension and a hypertensive fundus grade III or IV, can present itself as an emergency or an urgency. For a hypertensive emergency intravenously acting blood pressure lowering agents are almost always required, whereas an urgency can usually be treated with oral agents. In view of the danger of cerebral hypoperfusion, blood pressure reduction during the initial treatment phase of a hypertensive crisis should not be more than 20 to 25%. Agents that exert a controllable blood pressure lowering action are preferred. Controllable blood pressure lowering cannot be achieved with nifedipine capsules. The practice of biting and swallowing a nifedipine capsule for the treatment of a hypertensive crisis therefore is to be discouraged.

Acute Disease↗
PubMed1999

Sensitive and specific method for the simultaneous determination of natural and synthetic catecholamines and 3,4-dihydroxyphenylglycol in microdialysis samples.

The relatively new technique of microdialysis provides new possibilities for investigating in vivo the functioning of the sympathetic nervous system. The small sample volumes obtained, however, are a great challenge for analytical chemists. We report here a HPLC method for measuring in one run both natural and synthetic catecholamines [dopamine, (nor)epinephrine, alpha-methylnorepinephrine, isoproterenol and epinine] and the intraneuronal metabolite 3,4-dihydroxyphenylglycol in small microdialysis samples after derivatization with the fluorogenic agent 1,2-diphenylethylenediamine. No prior clean-up step is necessary. N-Ethylmaleimide is necessary for preventing an inhibitory action on derivatization occurring in in vivo microdialysis samples. The method can handle large numbers of samples, is sensitive (on-column detection limits 30 to 200 fg) and reproducible (RSD 1 to 7%). Recovery characteristics of the commercial microdialysis probe used (CMA/20) were extensively investigated both in vitro and in vivo at various perfusion rates; for practical purposes a rate of 2 microl/min and sampling at 10-min intervals was found to be workable and to give good and reproducible recoveries (50 to 70%).

Animals↗
PubMed1999

Endothelin-1 and blood pressure after inhibition of nitric oxide synthesis in human septic shock.

BACKGROUND: The systemic hypotension during human sepsis has been ascribed to increased production of nitric oxide (NO). Therefore, inhibitors of NO synthesis have been used in the treatment of hypotension in patients with septic shock. In addition, NO production may inhibit the synthesis and vasoconstrictor effects of endothelin-1 (ET-1). In this study, we tested whether ET-1 contributed to the vasopressor action of the NO synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME) in patients with severe septic shock. METHODS AND RESULTS: Compared with healthy volunteers, patients with septic shock had increased plasma levels of nitrite/nitrate (37+/-5 [SEM] versus 12+/-5 mmol/L, P<0.01), the stable end products of NO metabolism, and ET-1 (45+/-7 versus 3+/-2 pg/mL, P<0.001). Plasma ET-1 concentration was not related to plasma nitrite/nitrate concentration or blood pressure. Continuous infusion of L-NAME (1 mg. kg-1. h-1 IV) for 12 hours increased mean arterial pressure by 43+/-5% and systemic vascular resistance by 64+/-10% (both P<0.01). The increase in blood pressure and systemic vascular resistance correlated positively with the level of ET-1 (both P<0. 005) but not with plasma nitrite/nitrate level. L-NAME infusion did not result in significant changes in the plasma concentrations of ET-1 or nitrite/nitrate. CONCLUSIONS: NO and ET-1 may both play a role in the cardiovascular derangements of human sepsis. Although L-NAME does not increase ET-1 concentration in patients with septic shock, the vasopressor response induced by L-NAME depends on the plasma level of ET-1. These findings may indicate that inhibitors of NO synthesis unmask a tonic pressor response of ET-1 in human septic shock.

Blood Pressure↗
PubMed1999

Circulating semicarbazide-sensitive amine oxidase is raised both in type I (insulin-dependent), in type II (non-insulin-dependent) diabetes mellitus and even in childhood type I diabetes at first clinical diagnosis.

Plasma semicarbazide-sensitive amine oxidase is raised in patients with Type I (insulin-dependent) diabetes mellitus. It has been suggested that this enzyme is involved in the development of microvascular damage through its ability to convert amines (e.g. methylamine and aminoacetone) into aldehydes, hydrogen peroxide and ammonia. Plasma semicarbazide-sensitive amine oxidase was found to be equally raised both in patients with Type I diabetes (n = 73) and Type II (non-insulin-dependent) diabetes mellitus (n = 88) compared with control subjects (621 +/- 209 and 619 +/- 202 vs 352 +/- 102 mU/l, p < 0.0001) and to correlate in multiple regression analysis with HbA1c. Since the enzyme could protect the islets from the inhibitory effects of methylamine on insulin secretion, we also tested sera of 100 children, collected consecutively at first diagnosis of Type I diabetes, for semicarbazide-sensitive amine oxidase. The activity was greatly increased compared with serum values of 76 control (siblings) children (757 +/- 300 vs 455 +/- 138 mU/l, p < 0.0001), but not associated with HbA1c. Our study confirms the increase of plasma semicarbazide-sensitive amine oxidase in Type I diabetes and extends this finding to Type II diabetes as well as to childhood Type I at first clinical diagnosis. In the last case increased enzyme activities could serve to protect the islets from inhibitory effects of methylamine but cause damage by generation of hydrogen peroxide, aldehydes and ammonia. In the long run the increased enzyme activities could also contribute to vascular damage by direct cytotoxic action on endothelial cells, including increased oxidative stress and glycosylation of proteins.

Adolescent↗
PubMed1999

Role of sympathetic nervous system in cyclosporine-induced rise in blood pressure.

To clarify the role of the sympathetic nervous system in the development of cyclosporine A (CsA)-induced rise in blood pressure (BP), the effects of CsA on 24-hour ambulatory BP (ABP) were studied in patients with familial amyloid polyneuropathy (FAP) who underwent a liver transplantation. On the basis of autonomic function tests, patients with absent or mild-to-moderate sympathetic damage (Group A, n=11, age 29 to 43 years, disease duration 2 to 6 years) and patients with severe sympathetic damage (Group B, n=9, age 27 to 38 years, disease duration 3 to 9 years) were identified. Both groups were followed for 1 year. The daily doses of CsA and the CsA whole blood trough levels between the groups did not differ. Pretransplantation values of daytime and nighttime ABP were, respectively, 117+/-8/76+/-7 mm Hg and 108+/-12/68+/-9 mm Hg in group A and 107+/-6/66+/-4 mm Hg (P<0.05 group A versus group B) and 102+/-6/62+/-4 mm Hg in group B. In response to CsA, BP increased in all patients, but more so in patients of group B than in patients of group A. One year after transplantation, daytime and nighttime ABP had increased by 6+/-9/3+/-11% and 12+/-10/14+/-14% in group A and by 12+/-6/13+/-10% (P<0.05) and 21+/-11/27+/-21% (P<0.01) in group B. In both groups, the increase in nighttime ABP was greater than the increase in daytime ABP, which resulted in an attenuation or, even, a reversal of the diurnal BP rhythm. Because the rise in BP was greater in patients with more advanced sympathetic dysfunction, the sympathetic nervous system appears to counteract the CsA-induced rise in BP rather than causing it. This implies involvement of factors other than sympathetic activation in the pathogenesis of CsA-induced rise in BP in patients with familial amyloid polyneuropathy.

Adult↗
PubMed1998

Forearm vasorelaxation in hypertensive renal transplant patients: the impact of withdrawal of cyclosporine.

OBJECTIVE: To determine whether cyclosporine A-induced hypertension in renal transplant recipients is accompanied by impairment of endothelium-dependent vasodilatation, which has been suggested by in-vitro and in-vivo animal experiments. DESIGN AND METHODS: In-vivo endothelium-dependent and endothelium-independent vasodilatation, and plasma concentrations of vasoactive hormones in 16 renal transplant patients were determined while they were being treated with cyclosporine A, and 16 weeks later, after their treatment had been changed to azathioprine therapy. The vasodilator response of the forearm vascular bed was measured by strain gauge venous occlusion plethysmography during intra-arterial infusion of acetylcholine (endothelium-dependent vasodilatation) and nitroprusside (endothelium-independent vasodilatation). Postischemic reactive flow was measured after 10 min of arterial occlusion. In addition, plasma concentrations of norepinephrine, and the prostanoids prostaglandin E2 and thromboxane B2, and also concentration of cyclosporine A in blood, were measured. Glomerular filtration rate and renal blood flow were estimated 1 day before the plethysmography study during each treatment period. RESULTS: Upon changing from cyclosporine A to azathioprine treatment, mean arterial pressure fell significantly by 12+/-3% (P< 0.05). Glomerular filtration rate and renal blood flow increased by 13+/-5 and 19+/-8%, respectively (both P< 0.05), while renal vascular resistance fell by 48+/-11% (P< 0.01). Both baseline forearm blood flow and baseline forearm resistance did not change after conversion (5.7+/-0.7 versus 4.9+/-0.6 ml/100 ml/min, and 27.3+/-4.2 versus 26.2+/-3.2 arbitrary units). The absolute and relative forearm blood flow responses, and forearm vascular resistance responses to infusions of acetylcholine and nitroprusside were similar during treatments with cyclosporine A and azathioprine. Peak postischaemic forearm blood flow was 42+/-12% higher during cyclosporine A treatment than it was during azathioprine treatment (P< 0.05), but the minimal postischaemic forearm vascular resistance did not differ for these treatments. Plasma prostaglandin E2 and thromboxane B2 levels decreased by 34+/-7 and 45+/-8%, respectively, after changing treatment, but norepinephrine levels did not change. CONCLUSIONS: Our data indicate that cyclosporine A-induced hypertension in renal transplant recipients is not accompanied by an increase in forearm vascular resistance. In addition, changing from cyclosporine A to azathioprine treatment did not cause changes in endothelial vasodilator functioning, although mean arterial pressure decreased significantly. Our results do not support the hypothesis that attenuation of endothelial vasodilator functioning contributes to the development of cyclosporine A-induced hypertension.

Adult↗