Determinants of kidney function in Swedish families: role of heritable factors.

The aim of this study was to evaluate the determinants of kidney function and the role of heritable factors in a sample of 249 siblings free from known cardiovascular disease and without antihypertensive drugs belonging to 110 families. Four different measures and estimates of kidney function were considered. Blood pressure was recorded during 24 h by ambulatory blood pressure monitoring.

Novel mutations in the SLC12A3 gene causing Gitelman's syndrome in Swedes.

Purpose: Gitelman's syndrome (GS) is an inherited autosomal recessive disorder due to loss of function mutations in the SLC12A3 gene encoding the Na-Cl co-transporter (NCCT), the target of thiazide diuretics. The defective function of the NCCT, which normally is expressed in the apical membrane of the distal convolute tubule in the kidney, leads to mild hypotension, hypokalemia, hyperreninemic hyperaldosteronism, mild metabolic alkalosis, hypomagnesemia and hypocalciuria. Up to now, more than 100 mutations of the SLC12A3 gene have been described in GS patients.

Moderate salt restriction effectively lowers blood pressure and degree of salt sensitivity is related to baseline concentration of renin and N-terminal atrial natriuretic peptide in plasma.

Objective: The effect of salt restriction on blood pressure is under intense debate. We tested the effect of 100 mmol salt reduction on ambulatory blood pressure (ABP) in 46 Swedish individuals, 39 of whom completed the study, using a double-blind, placebo-controlled, cross-over design. Furthermore, we tested whether the basal plasma concentration of renin or N-terminal atrial natriuretic peptide (Nt-proANP) predict the degree of salt sensitivity.

Heritability of ambulatory and office blood pressure phenotypes in Swedish families.

Objective: The aim of this study was to estimate the heritability of 24-h ambulatory blood pressure and office blood pressure phenotypes in Swedish families.

Methods: We measured ambulatory and office blood pressure in 260 siblings without antihypertensive treatment from 118 families. Blood pressure heritability was estimated using standard quantitative genetic variance component analysis implemented in the 'SOLAR' software package after adjustment for significant covariates.

No evidence of a relation between 11beta-hydroxysteroid dehydrogenase type 2 activity and salt sensitivity.

Background: The ratio of urinary concentrations of tetrahydrocortisol plus allotetrahydrocortisol to tetrahydrocortisone [(THF + ATHF)/THE] reflects the activity of the enzyme 11beta-hydroxysteroid dehydrogenase type 2 (11BHSD2), which converts cortisol to cortisone in the kidney and thereby protects the mineralocorticoid receptor from the mineralocorticoid action of cortisol. The aim of the present study was to investigate whether 11BHSD2 activity is affected by salt intake and if it is related to salt sensitivity.

Methods: Concentrations of THF, ATHF, and THE in 24-h urine collections was determined by gas chromatography at baseline, after 1 week on a low salt diet (10 mmol/d), and after another week on a high salt diet (240 mmol/d) in 29 healthy subjects with heredity for hypertension.

A genome wide scan for early onset primary hypertension in Scandinavians.

With the aim of identifying hypertension susceptibility loci, we performed a genome wide scan in Scandinavian sib-pairs with early onset primary hypertension. To be classified as affected, a diagnosis of primary hypertension at age View Article and Find Full Text PDF

Effects of estrogen replacement therapy on abdominal fat compartments as related to glucose and lipid metabolism in early postmenopausal women.

The effects of estrogen replacement therapy on lipid and glucose metabolism as related to abdominal fat distribution were investigated in fifty-one healthy postmenopausal women aged 52-53 years. They were randomized to treatment with either estradiol 2 mg or placebo daily for three months in a double-blind design. Forty-six women continued with estradiol for another nine months in an open design with the addition of medroxyprogesterone for ten days every three months.

Plasma ProANP(1-30) reflects salt sensitivity in subjects with heredity for hypertension.

The aim of the present study was to investigate whether plasma concentration of proANP(1-30), the N-terminal fragment of the atrial natriuretic peptide prohormone, or 24-hour urinary excretion of urodilatin reflects the degree of salt sensitivity in hypertension-prone individuals. Plasma concentration of proANP(1-30) and urinary urodilatin excretion were determined at baseline, after 1 week on a low-salt diet (10 mmol/d) and after another week on a high-salt diet (240 mmol/d) in 30 healthy subjects with heredity for hypertension. Salt sensitivity was defined as the difference between mean arterial blood pressure after the high-salt diet and the mean arterial blood pressure after the low-salt diet.

Insulin sensitivity with respect to glucose metabolism in hypertension-prone men did not predict the blood pressure increase in 5 years.

Objectives: To evaluate peripheral insulin stimulated glucose uptake as a predictor for increase in blood pressure in hypertension-prone men.

Design: A follow-up study 5 years after a primary investigation that included an euglycaemic hyperinsulinaemic clamp to evaluate insulin sensitivity.

Subjects: Thirty-two men with a family history of hypertension (relatives) and 22 men with no hypertension in the family (controls).

Podocyte foot process broadening in experimental diabetic nephropathy: amelioration with renin-angiotensin blockade.

Aims/hypothesis: Changes in podocyte number and morphology have been implicated in the pathogenesis of proteinuria and the progression of human and experimental kidney disease. This study sought to examine podocyte foot process and slit pore architecture in experimental diabetic nephropathy and to determine whether such changes were modified with renoprotective intervention by blockade of the renin-angiotensin system.

Methods: The number of filtration slits per 100 microm of glomerular basement membrane was assessed by transmission electron microscopy and quantitated histomorphometrically in control animals and in rats with 24 weeks of streptozotocin-induced diabetes.

Metaiodobenzylguanidine (MIBG) scintigraphy and computed tomography (CT) in clinical practice. Primary and secondary evaluation for localization of phaeochromocytomas.

Objective: To determine the diagnostic value of metaiodobenzylguanidine (MIBG) scintigraphy compared with computed tomography (CT) for the localization of phaeochromocytomas in clinical practice.

Design: Retrospective comparison between MIBG scintigrams and CT for localization of phaeochromocytomas in all patients successively examined with MIBG scintigraphy in Malmö from 1984 until January 1997.

Setting: Malmö University Hospital, Sweden.

Hormone replacement therapy in healthy postmenopausal women: a randomized, placebo-controlled study of effects on coagulation and fibrinolytic factors.

Objectives: To evaluate effects of postmenopausal hormone replacement therapy (HRT) on von Willebrand factor, factor (F)VIII, factor (F)VII, fibrinogen, antithrombin (AT) III, prothrombin fragments 1 and 2, protein C, total and free protein S, plasminogen activator inhibitor-1 (PAI-1), tissue plasminogen activator (tPA) and resistance to activated protein C.

Design: Part 1: double blind randomized trial for 3 months. Part 2: open study for 9 months.

Relationship between abdominal fat compartments and glucose and lipid metabolism in early postmenopausal women.

The relationships between abdominal and pelvic fat compartments and glucose and lipid metabolism were investigated in early postmenopausal women. Fifty-five healthy, postmenopausal women aged 52-53 yr participated in the study. Fat distribution (intra-abdominal and sc abdominal fat, and intrapelvic and sc pelvic fat) was estimated by computed tomography.

Association between a variant in the 11 beta-hydroxysteroid dehydrogenase type 2 gene and primary hypertension.

The enzyme 11 beta-hydroxysteroid dehydrogenase type 2 (11BHSD2) converts cortisol to cortisone in the kidney, thereby protecting the mineralocorticoid receptor from the mineralocorticoid actions of cortisol. The syndrome of Apparent Mineralocorticoid Excess (AME), a rare monogenic form of early onset hypertension with autosomal recessive inheritance, is caused by homozygous or compound heterozygous loss of function mutations in the 11BHSD2 gene. Association has been reported between a microsatellite marker flanking the 11BHSD2 gene (D16S496) and primary hypertension.

Genetic variants of thiazide-sensitive NaCl-cotransporter in Gitelman's syndrome and primary hypertension.

Gitelman's syndrome is an autosomal recessive disorder characterized by electrolyte disturbances and low blood pressure. The disease is caused by homozygous or compound heterozygous inactivating mutations in the thiazide-sensitive NaCl-cotransporter gene leading to reduced renal sodium reabsorption. We report 4 patients with Gitelman's syndrome from southern Sweden, all in whom we identified compound heterozygous mutations in the thiazide-sensitive NaCl-cotransporter gene (Gly439Ser, Gly731Arg, Gly741Arg, Thr304Pro, and 2745insAGCA), of which the latter 2 have not been described before.

Hormone replacement therapy in healthy postmenopausal women. Effects on intraplatelet cyclic guanosine monophosphate, plasma endothelin-1 and neopterin.

Objectives: To evaluate beneficial effects of postmenopausal hormone replacement therapy (HRT) on endothelial function, measured as intraplatelet cyclic guanosine monophosphate (cGMP, mediator of nitric oxide), cyclic adenosine monophosphate (cAMP, mediator of prostacyclin) and plasma endothelin-1 (ET-1), and on monocyte activation, measured as plasma neopterin.

Design: Part 1: double-blind randomized trial for 3 months; part 2: open study for 9 months.

Setting: The study was performed at the Department of Endocrinology, University Hospital, Malmö, Sweden.

Effect of salt on insulin sensitivity differs according to gender and degree of salt sensitivity.

The aim of the present study was to investigate the effect of salt intake on insulin sensitivity and the relation between salt sensitivity and insulin sensitivity in genetically hypertension-prone individuals. Twenty-eight healthy subjects (13 men and 15 women) with a family history of hypertension were examined at baseline, after 1 week of salt restriction (10 mmol/d), and after 1 week of salt loading (240 mmol/d). Insulin sensitivity was measured with the hyperinsulinemic euglycemic clamp after the low- and high-salt diets.

Role of the Gly460Trp polymorphism of the alpha-adducin gene in primary hypertension in Scandinavians.

Previous studies have suggested that the Trp460 allele of the Gly460Trp polymorphism in the alpha-adducin gene is associated with salt sensitivity and primary hypertension. The present study was undertaken to evaluate if the Trp460 allele of this polymorphism is associated with primary hypertension in Scandinavians. To address this issue, 294 patients with primary hypertension and 265 normotensive control subjects from Sweden were examined and genotyped for the Gly460Trp polymorphism using polymerase chain reaction and restriction fragment length polymorphism methods.

Increasing neopterin and decreasing endothelin-1 in plasma during insulin infusion in women.

Leukocyte-derived inflammatory mediators and endothelial production of vasoconstrictive factors, such as endothelin-1, and vasodilatory and platelet anti-aggregatory factors, such as nitric oxide (NO) and prostacyclin (PGI2), may have a role in the pathogenesis of atherosclerosis. In this study we evaluated whether insulin affects the monocyte-derived inflammatory mediator neopterin and endothelin- in plasma (p), and NO and PGI2 mediators cyclic 3'-5' guanosine monophosphate (cGMP) and cyclic 3'-5' adenosine monophosphate (cAMP) in platelets. P-neopterin was measured by enzyme linked immunosorbent assay (ELISA), and p-endothelin-1, intraplatelet cAMP and cGMP were measured by radioimmunoassay (RIA) before and after euglycaemic hyperinsulinaemic clamping in 51 healthy postmenopausal women aged 53-54 years.

Heredity for hypertension influences intra-uterine growth and the relation between fetal growth and adult blood pressure.

Objective: To study whether heredity for hypertension influences intra-uterine growth and the relationship between fetal growth and adult blood pressure.

Design: Five-year prospective follow-up study with retrospective collection of data on size at birth and gestational age from obstetric records.

Setting: Centre of preventive medicine in Malmo, Sweden.

Reduced transcapillary fluid absorption from skeletal muscle and skin during hypovolaemia in insulin-dependent diabetes mellitus.

Objectives: Diabetes mellitus is associated with a high cardiovascular morbidity which has been linked to disturbances in microvascular function. This study was designed to examine the transcapillary fluid absorption during experimental hypovolaemia in type 1 diabetes.

Subjects: Twelve males with type 1 diabetes (age 25 +/- 3 years, duration 8 +/- 1 years) with no clinical microangiopathy and 12 healthy males (22 +/- 2 years).

Angiotensin converting enzyme inhibition and calcium antagonism attenuate streptozotocin-diabetes-associated mesenteric vascular hypertrophy independently of their hypotensive action.

Objectives: To investigate the relative roles of angiotensin II, bradykinin, and calcium-dependent pathways in the genesis of mesenteric vascular hypertrophy in experimental diabetes.

Design: Streptozotocin-induced diabetic Sprague-Dawley rats were randomly allocated to these treatments for 24 weeks: no treatment; ramipril at a hypotensive dose; ramipril plus the bradykinin type 2 receptor blocker icatibant; icatibant alone; ramipril at a low dose; the angiotensin II type 1 receptor antagonist, valsartan; the dihydropyridine calcium antagonist, lacidipine; and the nondihydropyridine calcium antagonist mibefradil.

Methods: Systolic blood pressure was serially measured every 4 weeks by tail-cuff plethysmography.

Insulin sensitivity, sodium-lithium countertransport and platelet free calcium concentrations in normotensive men with a family history of hypertension.

Peripheral glucose disposal (assessed with the euglycaemic-hyperinsulinaemic clamp technique), Na+-Li+ countertransport in erythrocytes and the cytosolic free Ca2+ concentration in platelets were determined in 36 men from families with essential hypertension in at least two close relatives and in 28 age- and weight-matched men from families without hypertension. All had diastolic blood pressure consistently below 90 mm Hg and a normal oral glucose tolerance test. The mean age of the study population as a whole was 37 years (range 24-46).

Mutations and variants of the epithelial sodium channel gene in Liddle's syndrome and primary hypertension.

Liddle's syndrome is a rare monogenic form of hypertension caused by truncating or missense mutations in the C termini of the epithelial sodium channel beta- or gamma-subunits. These mutations delete or alter a conserved proline-rich amino acid sequence referred to as the PY-motif. We report here a Liddle's syndrome family with a betaArg564X mutation with a premature stop codon deleting the PY-motif of the beta-subunit.