Oxidative stress and endothelin-1 in atherosclerotic renal artery stenosis and effects of renal angioplasty.

AIMS: To examine biomarkers of oxidative stress (oxs), and endothelin (ET)-1, in hypertensive patients with atherosclerotic renal artery stenosis (ARAS) and to evaluate the effect of percutaneous transluminal renal angioplasty (PTRA). METHODS: Baseline measurements were made immediately before renal angiography in patients with suspected ARAS (significant ARAS, n = 83, and non-RAS, n = 59) and in 20 healthy, matched controls. In patients with ARAS, analyses were repeated 4 weeks after PTRA. All patients were treated with statins and acetylsalicylic acid throughout. RESULTS: At baseline there were no significant differences between groups in biomarkers of oxs, whereas high-sensitivity C-reactive protein and blood leukocytes were significantly elevated in group ARAS versus both healthy controls and group non-RAS. Plasma levels of ET-1 and uric acid were significantly increased in group ARAS versus healthy controls prior to angiography and were significantly reduced compared to baseline 4 weeks after PTRA. PTRA had no significant effects on biomarkers of oxs, inflammation or serum creatinine concentrations. CONCLUSIONS: ARAS patients on treatment with antihypertensive agents, acetylsalicylic acid and statins showed elevated inflammatory indices but no increase in oxs. PTRA had no significant effects on inflammatory indices 4 weeks after intervention but reduced plasma ET-1 and uric acid.

Predictors of long-term beneficial effects on blood pressure after percutaneous transluminal renal angioplasty in atherosclerotic renal artery stenosis.

AIM: This retrospective study evaluated long-term effects of percutaneous transluminal renal angioplasty (PTRA) in atherosclerotic renal artery stenosis (ARAS), and predictors of benefit on blood pressure (BP). METHODS: During 1997-2003, 234 patients (age 69+/-11 years, 138 [59%] males) underwent PTRA for ARAS at Malmö Vascular Centre. Cure was defined as diastolic (D)BP<90 mmHg and systolic (S)BP <140 mmHg off antihypertensive medication. Improvement was defined as DBP <90 mmHg and/or SBP <140 mmHg on the same or reduced number of medications, or reduction in DBP of >or=15 mmHg with the same or reduced number of medications. Benefit was defined as cure or improvement. RESULTS: After PTRA, SBP and DBP decreased (P<0.001), and remained lower (P<0.001) until last follow-up after 4.1+/-3.3 years. Antihypertensive medication decreased (P<0.001), and remained lower at one month (P<0.001), one year (P<0.01), and last follow-up (P<0.05). Renal function was unchanged until last follow-up, when it deteriorated (P<0.001). Patients showing benefit of PTRA on BP at last follow-up (N.=150 [64%]) used more antihypertensive drugs before PTRA (P=0.012), especially angiotensin converting enzyme inhibitors (ACEi) or angiotensin II receptor blockers (ARBs) (P=0.010), and diuretics (P=0.015). In logistic regression, use of ACEi or ARBs failed to reach significancy (P=0.054). Patients dying during follow up (N.=100 [43%]) showed higher age (P<0.0001) and s-creatinine (P<0.0001), lower glomerular filtration rate (P<0.0001), and higher frequency of diabetes mellitus (P<0.005). In logistic regression only age (P=0.009) and diabetes mellitus (P=0.014) predicted mortality. CONCLUSIONS: We confirmed beneficial effects on BP with PTRA in ARAS. ACEi, ARB and diuretic treatment before PTRA predict favourable long-term BP-response in univariate analysis.

Are there differences of inflammatory bio-markers between diabetic and non-diabetic patients with critical limb ischemia?

AIM: This observational study was undertaken in order to analyse whether any differences could be detected between diabetic and non-diabetic patients with critical limb ischemia (CLI) concerning the inflammatory response. METHODS: A total number of 259 consecutive patients with CLI were treated between October 2001 and January 2003. RESULTS: Among the 259 patients, 135 (52%) had diabetes, previously known in 123, and detected during hospitalization in 12. The diabetic patients more often showed gangrene (P<0.05) and infra-inguinal atherosclerosis (84% vs 67%, P=0.001). The patients with diabetes showed a better lipid profile (total cholesterol 4.6 vs 5 mmol/L, P=0.006 and lower LDL-cholesterol (2.7 vs 3.1 mmol/L, P=0.010) despite the same frequency of statin treatment. They showed a higher creatinine (149 vs 117 micromol/L, P=0.0003) than the non-diabetic patients. Of the inflammatory markers, C-reactive protein (CRP) was equally elevated in both groups. Tumor necrosis factor-a (TNF-a) was increased among the diabetic patients (2.6 vs 1.8 pg/mL, P<0.05), and this difference was most evident in those with gangrene. Neopterin was also higher among the diabetic patients (31 vs 21 mmol/L, P<0.01), but CD40L was not different between groups. CONCLUSIONS: Diabetes mellitus was very common in CLI patients, and more often combined with renal impairment and infra-inguinal atherosclerosis. The inflammatory markers TNF-a and neopterin were elevated in patients with diabetes as compared to non-diabetic patients, but this difference cannot explain why CLI is 10 times more frequent in diabetic patients.

Revascularisation of renal artery stenosis caused by fibromuscular dysplasia: effects on blood pressure during 7-year follow-up are influenced by duration of hypertension and branch artery stenosis.

Fibromuscular dysplasia (FMD) mainly affects renal arteries. Percutaneous transluminal renal angioplasty (PTRA) and surgery are effective treatments, but long-time follow-up is lacking. Retrospective follow-up for 7.0+/-4.7 years of 69 consecutive patients (age 44+/-13 years) treated for hypertension due to FMD, 59 patients underwent PTRA and eight patients surgery. In two patients no PTRA was performed. Technical success was achieved in 56 (95%) patients undergoing PTRA and all eight undergoing surgery. After successful PTRA, both systolic and diastolic blood pressures (SBP and DBP) had decreased at discharge (from 174+/-33/100+/-13 to 138+/-19/80+/-15 mmHg; P<0.0001), and remained lower at 1 month, 1 year, and last follow-up after 7.0+/-4.7 years (140+/-25/83+/-12 mmHg; P<0.0001). Serum-creatinine had decreased both at 1 year (from 84+/-28 to 75+/-13 micromol/l; P=0.0030) and last follow-up (75+/-16 micromol/l; P=0.0017). The number of antihypertensive drugs decreased (from 2.3+/-1.2 before PTRA to 1.4+/-1.3 at discharge and at 1 month; P<0.0001, and 1.6+/-1.5 at last follow-up; P=0.0011). SBP decreased more after PTRA among patients with FMD only in the main renal artery than in those with branch artery involvement (43+/-29 vs 20+/-41 mmHg; P=0.0198). Beneficial effects on BP, creatinine and antihypertensive drugs also occurred after surgery. Patients on antihypertensive drugs at last follow-up had longer hypertension duration before PTRA than those without (5.9+/-7.7 vs 1.8+/-4.1 years; P=0.0349). Cure was achieved in 16 (24%), improvement in another 26(39%), and benefit in 42(63%). In conclusion, renal artery FMD, PTRA and surgery have beneficial long-term effects, negatively affected by hypertension duration and branch artery involvement.

Suboptimal treatment of risk factor for atherosclerosis in critical limb ischemia.

AIM: The epidemiology of critical limb ischemia (CLI) is insufficiently studied, and treatment of risk factors for atherosclerosis has received less attention in CLI patients than in patients with coronary or precerebral atherosclerosis. The aim of this study was to establish the incidence of CLI and the quality of risk factor treatment in Swedish CLI patients. METHODS: During 14 months, 316 consecutive CLI patients were referred to the Malmo Department of Vascular Diseases. Two hundred and fifty-nine (82%) consented to evaluation of intercurrent disease, medication, ankle and arm blood pressures (BP), plasma glucose and lipid levels, p-homocysteine, cardiolipin antibodies and activated protein C (APC)-resistance. RESULTS: The incidence of CLI was 38/100,000 inhabitants/year. Patient age was 75 +/- 10 years, and BP 147 +/- 26/75 +/- 14 mmHg. Systolic or diastolic BP above recommended levels (140/90 mmHg) occurred in 137 (53%) patients. P-cholesterol was 4.8+/-1.2 mMol/L, but cholesterol above recommended level (5 mMol/L) or LDL above recommended level (3 mMol/L) occurred in 125 (48%) patients. Only 24% of patients met national recommendations for both BP and lipid levels. Diabetes mellitus was previously known in 123 (47%) patients, and another 12 (5%) patients showed diabetic fasting glucose levels during the hospital stay. Eighty-four (32%) patients were active, and 72 (28%) were former smokers. Myocardial infarction or angina pectoris had previously been diagnosed in 123 (47%) patients. P-homocysteine was 17 +/- 7 _mol/l, cardiolipin antibodies occurred in 71 (27%) and APC-resistance in 34 (13%) patients. CONCLUSIONS: Patients with CLI show high comorbidity in vascular diseases and high prevalence of modifiable risk factors for atherosclerotic vascular disease. The use of evidence-based medical therapy is suboptimal in this high-risk group.

Insulin and renal sodium retention in hypertension-prone men.

Insulin-stimulated peripheral glucose uptake and insulin-induced renal tubular sodium reabsorption were investigated in normotensive men with a family history of hypertension (relatives, n = 35) compared with age- and body mass index-matched normotensive men with no family history of hypertension (controls, n = 23). The effect of insulin on the renin-aldosterone system was also studied. The euglycemic hyperinsulinemic clamp technique was used to measure peripheral glucose uptake (insulin sensitivity index). Renal clearance of 51Cr-labeled EDTA, sodium, and lithium was used to calculate fractional excretion of sodium and fractional proximal and distal tubular reabsorption of sodium before and during insulin infusion. The insulin sensitivity index was lower in relatives than in controls. Fractional excretion of sodium was reduced, and fractional proximal and distal tubular reabsorption of sodium were increased to the same extent in both groups during insulin infusion. Fractional distal tubular reabsorption of sodium was positively correlated to the reduction of serum potassium in all individuals. Plasma renin activity increased to the same extent in both groups, whereas plasma aldosterone was reduced only in controls. In conclusion, the impaired insulin-stimulated glucose uptake in peripheral tissues in normotensive sons of hypertensive families was accompanied by retained insulin-induced tubular sodium reabsorption. The lack of suppression of aldosterone secretion in these individuals may enhance sodium retention.

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. Insulin sensitivity was assessed by euglycemic hyperinsulinemic clamp. In a multiple regression analysis, the size of the intra-abdominal fat compartment was the only significant predictor of insulin sensitivity (r(2) = 24%; P = 0.0002). Plasma triglycerides were closely related to the size of the intra-abdominal fat compartment (r(2) = 26%; P < 0.0001), whereas plasma free fatty acid concentrations only correlated to the size of the sc abdominal fat compartment (r(2) = 18.5%, P = 0.001). In early postmenopausal women the amount of the intra-abdominal fat strongly influences insulin sensitivity and plasma triglyceride levels, whereas plasma free fatty acids are closely related to the amount of the sc abdominal fat. Accordingly, from a metabolic standpoint it seems most essential to reduce intra-abdominal fat in postmenopausal women.

Insulin and forearm vasodilation in hypertension-prone men.

Insulin-stimulated peripheral glucose uptake and insulin-mediated forearm vasodilation were investigated in 38 normotensive men with a family history of hypertension (relatives) compared with 27 age- and body mass index-matched normotensive men with no family history of hypertension (control subjects). The euglycemic hyperinsulinemic clamp technique was used to measure peripheral glucose uptake (insulin sensitivity index) and the metabolic clearance rate of insulin. Intra-arterial blood pressure and forearm blood flow were determined simultaneously, and forearm vascular resistance was calculated. The insulin sensitivity index was lower in relatives than in control subjects. The metabolic clearance rate of insulin was reduced and did not correlate to glucose disposal in the relatives as opposed to the control subjects. Forearm blood flow increased and forearm vascular resistance decreased to a similar extent in the two groups during the clamp. The vasodilator response was positively correlated to glucose disposal only in the relatives. In conclusion, impaired insulin-stimulated peripheral glucose uptake in normotensive sons from hypertensive families was accompanied by retained insulin-mediated forearm vasodilation. Thus, skeletal muscle blood flow supply does not seem to be the major determinant for glucose disposal. On the other hand, the positive correlation between glucose disposal and decrease in forearm vascular resistance in the relatives suggests that insulin-mediated vasodilation may be a limiting factor for peripheral glucose uptake in insulin-resistant individuals.

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. This family shows marked phenotypic variation in blood pressure, serum potassium levels, and age of onset of hypertension. Given the similarity with primary hypertension, changes in the C termini of the beta- or gamma-subunits may contribute to the development of primary hypertension or to hypertension associated with diabetic nephropathy. Accordingly, the coding sequences for the cytoplasmic C termini of the beta- and gamma-subunits were screened for mutations with the use of polymerase chain reaction, single-strand conformation polymorphism, and direct DNA sequencing in 105 subjects with primary hypertension and 70 subjects with diabetic nephropathy. One frequent polymorphism was identified, but its frequency did not differ among subjects with primary hypertension, subjects with diabetic nephropathy, or control subjects. Two of the 175 subjects with primary hypertension or diabetic nephropathy showed variants that were not present in 186 control subjects. None of the variants changed the PY-motif sequence. In conclusion, a betaArg564X mutation is the likely cause of Liddle's syndrome in this Swedish family, but it is unlikely that mutations in the beta- and gamma-subunit genes of the epithelial sodium channel play a significant role in the pathogenesis of primary hypertension or diabetic nephropathy.

Coagulation and fibrinolytic factors in normotensive hypertension-prone men.

OBJECTIVE: To evaluate whether a family history of hypertension is associated with disturbances in the coagulation and fibrinolytic systems. SUBJECTS: Thirty-five normotensive men with a family history of hypertension (relatives) and 27 age- and body mass index-matched controls with a family history (controls). METHODS: Insulin sensitivity was determined with a euglycaemic hyperinsulinaemic clamp technique. Maximal oxygen uptake was estimated from a submaximal work test. Blood samples were analysed for several coagulation and fibrinolytic factors. RESULTS: Relatives had higher plasma levels of plasminogen activator inhibitor-1. Levels of plasma factor VII, prothrombin fragments 1 and 2, fibrinogen and von Willebrand factor antigen did not differ significantly between the groups. However, antithrombin III, protein C and protein S levels were higher in the relatives than in the controls. Coagulation and fibrinolytic factors correlated to waist circumference, insulin sensitivity, maximal oxygen uptake and serum triglycerides level. CONCLUSIONS: Normotensive men with a family history of hypertension have an inhibited fibrinolysis, but also higher levels of several anticoagulant factors. The clinical application of these findings for the future development of cardiovascular disease warrants additional studies.

Insulin resistance is coupled to low physical fitness in normotensive men with a family history of hypertension.

OBJECTIVE: To investigate insulin sensitivity and the influence of level of physical fitness in men with a family history of hypertension and in control subjects. DESIGN: Insulin sensitivity was determined and physical fitness estimated in 39 normotensive, glucose-tolerant men with a family history of hypertension (Relatives group) and in 29 age- and body mass index-matched normotensive men with no such family history (Controls group). METHODS: The euglycaemic hyperinsulinaemic clamp technique (steady-state insulin concentration approximately 100 mU/l) was used to determine insulin sensitivity. Physical fitness, measured as maximal oxygen uptake, was estimated from the heart rate response to a submaximal exercise test. RESULTS: Insulin sensitivity index and estimated maximal oxygen uptake were lower in the Relatives than in the Controls. There was a positive correlation between insulin sensitivity and maximal oxygen uptake in both groups. In the Controls there was a negative correlation between insulin sensitivity and waist:hip ratio, but this relationship was not found in the Relatives. CONCLUSIONS: The present findings indicate that reduction of insulin sensitivity precedes the development of high blood pressure and may be coupled to low physical fitness. As abdominal fat distribution seems not to be related to insulin sensitivity in subjects with a family history of hypertension, changes in muscle fibre composition or muscle glucose metabolism, or both, might explain the lower insulin sensitivity and physical fitness in the Relatives.

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. SUBJECTS: Thirty normotensive men with and 27 without heredity for hypertension were investigated in 1990, and the majority (n = 28 and n = 20, respectively) in 1995 also. MAIN OUTCOME MEASURES: Two measures of intra-uterine growth were compared between the groups and related to adult systolic blood pressure: the birth weight deviation from the expected birth weight based on ultrasonically derived intra-uterine growth curves, and the degree of thinness at birth (ponderal index = weight/length3). RESULTS: The birth weight deviation in men with heredity for hypertension differed significantly from that in men without such heredity (%) (-6.9+/-12.0 versus +7.3+/-18.4; P = 0.002). Ponderal index was somewhat lower in the men with than in those without heredity for hypertension, but the difference did not reach statistical significance (kg/m3) (25.9+/-2.6 versus 27.0+/-2.2; P = 0.08). In the group with heredity for hypertension, systolic blood pressure correlated inversely with ponderal index both in 1990 (r = -0.44; P = 0.01) and 1995 (r = -0.49; P = 0.009), and the 5-year increase in systolic blood pressure correlated inversely with the birth weight deviation (r = -0.38; P = 0.04). No such correlations were found in the group without heredity for hypertension. CONCLUSION: Our results suggest that genetic factors contributing to the development of hypertension may influence intra-uterine growth.

Distribution of the methyl acceptor proteins within platelet granules.

Fractionation of platelet alpha-granules and dense bodies demonstrated that methyl acceptor proteins (MAP) were present in the alpha-granule fractions, but seemed to be low or absent in the dense body fraction. MAP activity in four intragranular proteins (albumin, fibrinogen, beta-thromboglobulin and platelet derived growth factor) was low or absent and could not explain the difference in methyl acceptor proteins distribution between alpha-granules and dense bodies.

Efflux of granule constituents from platelets exposed to different mechanical forces.

The efflux of 14C-norepinephrine, 3H-serotonin and beta-thromboglobulin from platelets was compared with the extent of lysis in two different systems of incubation, in which Ca2+ and conventional platelet activating agents were omitted. In the first system platelets were incubated in buffer at 37 degrees C and gently shaken. Cell lysis was low and efflux of 14C-norepinephrine was 71-97% of total initial uptake after 24 hours. In the other system rotating plastic tubes at 20 degrees C were used which exposed the platelets to higher mechanical stress. Cell lysis and aggregation was already high after 10-30 minutes, but the efflux of 14C-norepinephrine and 3H-serotonin was lower and not parallel to cell lysis. The release of 14C-norepinephrine was higher than that of 3H-serotonin in both systems. There was a considerable release of beta-thromboglobulin from platelets remaining in plasma despite of a constant pH. These findings indicate that platelet lysis is independent of the release of platelet granule constituents.

Effects of thrombin, acetyl salicylic acid and prostaglandins on spontaneous efflux of norepinephrine and beta-thromboglobulin from platelets in calcium/magnesium deficient environment.

The effect of different substances on the spontaneous efflux of 14C-norepinephrine (14C-NE) and beta-thromboglobulin (beta TG) from platelets in Ca2+ - and Mg2+ - free buffer was tested. Addition of increasing concentrations of thrombin (0.015-0.625 U/ml) resulted in an immediate increase of 14C-NE detectable in the supernatants, but the slopes of the efflux curves from 10 min after thrombin addition were almost identical and parallel with the slope before thrombin addition. Also beta-thromboglobulin was steadily released after thrombin addition. Prostaglandin E1 and prostacyclin in concentrations that gave a 30-fold increase in cAMP accumulation resulted in a moderate decrease in efflux of 14C-NE from 10 to 30 min but did not influence the efflux thereafter up to 80 min. Acetyl salicylic acid in vivo and in vitro (200-500 mumol/l) did not influence the efflux of 14C-NE or beta TG. The conclusions are that factors known to exert considerable effects on aggregation, desaggregation and acute release produce only transitory effects in a Ca2+ - and Mg2+ - free environment and that the basal efflux of alpha-granule components seems to be a stable process.

Long-term effects on insulin sensitivity and sodium transport in glucose-intolerant hypertensive subjects when beta-blockade is replaced by captopril treatment.

Long-term effects on insulin sensitivity and leucocyte sodium transport were studied in 42 glucose-intolerant hypertensives on beta-blockers, randomly assigned to continuous beta-blockade (beta group) or a switch to captopril treatment (mean daily dose 69.1 mg) (ACE group). In the ACE group, despite a tendency towards improvement, glucose uptake during the euglycaemic insulin clamp procedure did not change significantly from the baseline value of 4.0(0.5-12.9) mg/kg/min, values at 6 and 12 months being 4.8(1.3-14.7) and 4.4(1.5-9.8) mg/kg/min, respectively: the corresponding values for the beta group were 4.2(1.1-15.3), 3.6(1.2-8.9) and 4.0(1.5-12.0) mg/kg/min. The 22Na efflux rate constant, both baseline and follow-up values, was similar in both groups, and unrelated to insulin sensitivity. Owing to the surprisingly great variation in peripheral glucose uptake, the subgroup with values below the median for the population as a whole (4.9 mg/kg/min) was evaluated separately: those switched to captopril treatment manifested a 60% improvement in glucose disposal at 6 months and persisting at 12 months, the respective values being 2.1(0.5-4.8) (baseline), 3.5(1.3-6.3) and 3.4(1.5-6.1) mg/kg/min, (P = 0.012). The body mass index (BMI) was not significantly affected. Values for BMI, peripheral insulin and triglycerides were higher in the subgroup with glucose disposal below the median than in the subgroup with values above the median. Correlation between BMI and glucose uptake was highly significant (r = -0.75, P = 0.0001). The present findings suggest that captopril may be a better alternative than beta-blockers for treating the highly insulin-resistant, glucose-intolerant patients, predominantly to be found among the overweight.

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). All were normotensive and had a normal glucose tolerance. MAIN OUTCOME MEASURES: Change in blood pressure over 5 years and its relation to the values obtained in the basal investigation. RESULTS: Systolic and diastolic blood pressure increased in both groups during the 5 years, but diastolic blood pressure increased more in relatives than in controls (11 mm Hg vs 5 mm Hg, P = 0.03). The change in diastolic blood pressure was correlated to basal BMI (r = 0.43, P = 0.02) only in controls. There were no correlations between the change in blood pressure during the 5 years and basal glucose disposal nor to any of the other basal parameters in either relatives or controls. CONCLUSIONS: Insulin sensitivity did not predict the change in blood pressure during the 5 years either in hypertension-prone men or in controls, nor did anthropometrical measurements, basal and stimulated insulin and maximal oxygen uptake. The blood pressure increase was related to basal BMI only in controls.

Low testosterone and insulin resistance in hypertension-prone men.

The aim of the study was to elucidate the relationship between peripheral insulin sensitivity and testosterone and sex hormone binding globulin (SHBG) in the development of hypertension. An euglycaemic hyperinsulinaemic clamp was performed to determine insulin sensitivity and sex steroid hormones and SHBG were analysed in 35 normotensive men with a family history of hypertension (relatives) and 27 age and body mass index matched controls (controls). Relatives had lower concentrations of serum total testosterone and SHBG, and lower insulin sensitivity compared to controls. Free testosterone concentrations were the same in both groups. Relatives had lower maximal oxygen uptake compared to controls. Total testosterone and SHBG were correlated to basal insulin concentration and insulin sensitivity in relatives, but not in controls. In stepwise regression analysis, total testosterone explained 37% and walst circumference 6% of the variation of insulin sensitivity in relatives, and walst circumference explained 29% in controls. When substituting testosterone with SHBG in this model, SHBG explained 48% of the variation in insulin sensitivity in relatives. The finding of a closer relationship between insulin sensitivity and SHBG than between insulin sensitivity and total testosterone suggests that the SHBG level is primarily influenced by insulin sensitivity in the relatives.

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). Insulin sensitivity index values (glucose disposal/serum insulin concentration during the clamp) were lower in the familial hypertension group than in the control group, but the two groups did not differ in Na+-Li+-countertransport, or in the platelet cytosolic free Ca2+ concentration which was correlated to the waist: hip circumference ratio in both groups (r = 0.38 and r = 0.49, respectively). The present findings do not support the hypothesis that an increase in Na+-Li+ countertransport activity or the platelet cytosolic free Ca2+ concentration is a marker of insulin resistance in hypertension prone men.

Sustained beneficial effects on blood pressure during long time retrospective follow-up after endovascular treatment of renal artery occlusion.

We retrospectively evaluated short- and long-term effects of percutaneous transluminal renal angioplasty (PTRA) with or without stent placement of renal artery occlusion (RAO) upon blood pressure (BP), serum (s)-creatinine, and the need for antihypertensive treatment in 34 RAO patients who underwent PTRA during 1996-2002. In 24/34 (71%) treatment was considered technically successful, 22/24 (92%) were treated with PTRA + stent, two with only PTRA. Patients were followed for mean 2.6 (range 0-8) years, during which 14/34 (41%) patients died. In all 34 patients, systolic and diastolic BP (SBP and DBP) before treatment were 184 +/- 30/95 +/- 15 mmHg and had decreased at discharge (to 157 +/- 21/80 +/- 10 mmHg; P < 0.001 for both SBP and DBP), and remained lower after 1 year (154 +/- 20/83 +/- 7 mmHg; P < 0.001 for SBP and P < 0.01 for DBP), and at last follow-up (148 +/- 20/80 +/-12 mmHg; P < 0.001 for both SBP and DBP). No changes occurred in s-creatinine or the number of antihypertensive drugs. Similar results were seen in the subgroup of 24/34 (71%) patients in whom treatment was technically successful. Among the 24 patients undergoing technically successful PTRA, absence of nephrosclerosis (P = 0.035) and a shorter duration of hypertension (P = 0.020) predicted favourable clinical outcome. No adverse effects upon s-creatinine or the need for antihypertensive medication were seen in patients in whom treatment was considered a technical failure. Seven of these patients were treated with PTRA of another renal artery than the occluded, or with embolisation. In conclusion, RAO can be treated with endovascular techniques. Technically successful results with decreasing blood pressure levels were obtained in 71% of patients.