Heritable forms of hypertension

Among the causes of secondary hypertension are a group of disorders with a Mendelian inheritance pattern. Recent advances in molecular biology have unveiled the pathogenesis of hypertension in many of these conditions. Remarkably, the mechanism in every case has proved to be upregulation of sodium (Na) reabsorption in the distal nephron, with accompanying expansion of extracellular volume. In one group, the mutations involve the Na-transport machinery in distal tubule cells themselves: the distal convoluted tubule (DCT) cell and the principal cell of the collecting duct. Examples include Liddle’s syndrome, with an activating mutation of epithelial Na channel (ENaC); two types of Gordon’s syndrome, with mutations in two regulatory kinases [with no lysine (K) serine/threonine protein kinases (WNK)1 or WNK4]; and apparent mineralocorticoid excess (AME), with an inactivating mutation in the glucocorticoid-metabolizing 11β-hydroxysteroid dehydrogenase type 2 enzyme (11HD2). In another group, abnormal adrenal steroid production leads to inappropriate stimulation of the mineralocorticoid receptor (MR) in the distal nephron. The pathophysiology may involve inappropriate production of aldosterone [in glucocorticoid-remediable aldosteronism (GRA) and familial hyperaldosteronism type II (FH II)], of cortisol (in familial glucocorticoid resistance), or of other steroid metabolites (in congenital adrenal hyperplasia and GRA). In contrast to earlier beliefs, hypertension in many of the inherited disorders may be mild, and electrolyte and acid-base abnormalities are often not present. Monogenic hypertension should therefore enter the differential diagnosis of any child or adolescent with hypertension. Plasma renin activity (PRA) is the appropriate screening tool for all types of inherited hypertension.     

Changes of vasoactive substances following embolization for renal cell carcinoma

Renal arterial embolization and subsequent nephrectomy or nephrectomy alone were performed in 34 patients with renal cell carcinoma. Renal arterial embolization caused a blood pressure elevation concomitant with an increase in plasma renin activity (PRA), urinary aldosterone excretion or urinary prostaglandin (PGE₂) excretion. Subsequent nephrectomy normalized hypertension and reduced the levels of these vasoactive substances. There were significant relationships between the increase in mean blood pressure and the increase in PRA, the increment in mean blood pressure and the increment in urinary aldosterone excretion, and the increase in PRA and increase in log urinary PGE₂ excretion following embolization. These evidences suggest that enhancement of the renin-angiotensin-aldosterone system participates in the development of hypertension following embolization, and increased PRA may play an important role in the release of urinary PGE₂.     

Hypertension in Primary Glomerulonephritis Without Renal Insufficiency

Hypertension is frequently present in glomerunephritis withoutrenal insufficiency but its pathogenesis is poorly understood.Eighty-five patients with glomerulonephritis and normal renalfunction, including 55 hypertensive patients, and 24 normalsubjects were studied to obtain data on the mechanisms responsiblefor hypertension. Plasma renin activity (PRA), plasma noradrenaline,total exchangeable sodium, and urinary prostaglandin E (PGE)were determined. Moreover, the autonomic nervous system wasexplored with the following tests: tilt test, diving reflex,lying down, and deep breathing tests. In 15 of the 30 normotensivepatients with glomerulonephritis, PRA was measured after theadministration of propranolol and then indomethacin. No significantdifferences were found in the mean values of PRA, plasma noradrenaline,total exchangeable sodium, urinary PGE, and autonomic nervoussystem behaviour between glomerulonephritis patients with andwithout hypertension or between hypertensive glomerulonephritispatients and control subjects. In many of the normotensive glomerulonephritispatients we found an elevated PRA that was normalised by propanololbut not by indomethacin. In summary, hypertension in glomerulonephritis is not associatedwith abnormalities in the sodium balance, with renin-angiotensinor with autonomic nervous system abnormalities. A renin hypersecretionseems to be present only in some normotensive patients withglomerulonephritis.     

Family history of end-stage renal disease among hemodialyzed patients in Poland

BACKGROUND: In previous reports of end-stage renal disease (ESRD) patients, family history of ESRD was associated with race, younger age, higher education levels and ESRD etiology. This study aimed to analyze how often Polish caucasian dialysis patients reported relatives with ESRD, and to evaluate which risk factors are associated with family history of ESRD. METHODS: 4808 ESRD patients provided data about renal disease etiology, diabetes and hypertensive status of first- and second-degree relatives, socioeconomic status and education level. RESULTS: Reported ESRD etiologies were: chronic glomerular disease, 19.4 %; diabetic nephropathy, 11.3%; interstitial nephritris, 11.2%; hypertension, 7.8%; polycystic kidney disease (PKD), 7.1%; other or no response, 40.0%. Positive ESRD family history was reported by 745 patients (15.5%); positive history of diabetes, 932 (19.4%); hypertension, 1904 (39%). Positive ESRD family history according to kidney disease etiology was: PKD, 53.1%; glomerulonephritis, 12%; diabetic nephropathy, 11.9%; hypertension, 11.8%; interstitial nephritis, 10.8%. PKD as ESRD etiology (odds ratio (OR) 8.06, 95% confidence interval (CI) 6.35-10.23, p < 0.0001), positive family history of diabetes (OR 1.64, 95% CI 1.34-1.99, p < 0.0001) and positive history of hypertension (OR 1.64, 95% CI 1.39-1.95, p < 0.0001), were independently associated with positive ESRD history. Patients with later ESRD onset had a less frequent positive ESRD family history: for ESRD < 45 yrs, 16% (OR 1.0); 45-64 yrs, 14.4% (OR 0.83, 95% CI 0.70-0.99); > or = 65 yrs, 9.2 % (OR 0.5, 95% CI 0.35-0.72). CONCLUSIONS: Results of our study strongly support the contention that familial predisposition contributes to ESRD development.     

Familial and genetic risk of transitional cell carcinoma of the urinary tract

Environmental exposures, including tobacco smoke and occupational exposure to aromatic amines, have been implicated in bladder cancer etiology. However, the pathogenesis of urinary bladder transitional cell carcinoma remains incompletely defined. In epidemiologic studies, family history confers a 2-fold increase in bladder cancer risk, but it is uncertain whether this represents evidence of a genetic and/or a shared environmental basis for familial aggregation. Polymorphisms in genes involved in the metabolism of environmental toxins (e.g., NAT2) clearly modify individual susceptibility to bladder cancer. A genetic predisposition has also been suggested by case reports describing multiple-case families, and the development of bladder cancer in association with several well-described Mendelian disorders (e.g., HNPCC, retinoblastoma). Here we update a previously reported family, report a new multiple-case kindred, critically review previously reported bladder cancer families, and the epidemiologic literature related to family history of transitional cell carcinoma of the urinary tract (TCCUT) as a risk factor, as well as provide a brief summary of genetic factors that have been implicated in TCCUT risk. We conclude that familial TCCUT is either very uncommon or significantly under-reported, perhaps on the assumption that this is an environmental rather than a genetic disorder. The interaction between multiple genetic and environmental factors has made it challenging to identify genetic components responsible for many common diseases; therefore, a proposed genome-wide association study (GWAS) for urinary bladder cancer may help to clarify the etiologic role of the candidate genetic pathways reviewed here, as well as characterize gene/environment interactions that contribute to TCCUT carcinogenesis.     

Steroid-induced hypertension in patients with nephrotic syndrome

In 35 initially normotensive patients with chronic glomerulonephritis and lupus nephritis (including 27 patients with nephrotic syndrome; NS), blood pressure (BP), urinary sodium excretion, plasma renin activity (PRA), plasma aldosterone level (PA), urinary aldosterone excretion (Au and blood volume were measured before and during prednisolone treatment. In 7 patients (all with NS) steroid-induced hypertension has developed. The patients prone to develop hypertension were hypervolemic nephrotics with initial depression of PRA, PA, Au, and severe sodium retention. In these patients prednisolone did not produce diuresis of natriuresis nor did it decrease proteinuria. In normo- and hypovolemic patients prednisolone produced significant diuresis and natriuresis and failed to induce hypertension. Thus, two types of response to prednisolone could be observed in patients with NS.     

Characteristics of children with primary hypertension seen at a referral center

Primary hypertension is well known to occur in children, but the characteristics of such children are changing due to the influence of the obesity epidemic. In view of this, we conducted a cross-sectional study of 70 children [age 13.3±4 years (mean ± SD)] with primary hypertension referred to a specialized pediatric hypertension clinic. Secondary hypertension had been excluded after a standardized diagnostic evaluation. Isolated systolic hypertension was present in 62.9% of subjects. Family history of hypertension was present in 86.2%, and 52.9% were obese (BMI 95th percentile). BMI was weakly correlated with systolic BP (r =0.28,P =0.10) and was significantly correlated with total cholesterol (r =0.36,P =0.005) and triglycerides (r =0.42,P =0.01). Mean plasma renin activity (PRA) was 3.1±2.7 ng/ml/h. PRA was correlated with diastolic but not systolic BP. Patients with high PRA had higher diastolic BP and lower BMI compared to those with low PRA. Left ventricular hypertrophy was present in 24%. Mean 24-h systolic BP load by ambulatory BP monitoring was 52±24%; mean 24-h diastolic BP load was 18±16%; BP loads were greater in patients with high PRA. These data suggest that primary hypertension in children is characterized by systolic BP elevation, positive family history and obesity. Hyperlipidemia accompanies primary hypertension in obese children, and left ventricular hypertrophy is common. Patients with high PRA have more severe BP elevation. Future studies should focus on further defining the pathophysiology of primary hypertension in children, including the roles of renin and insulin resistance, so that improved methods of prevention and treatment can be developed.This work was presented in abstract form at the European Society of Pediatric Nephrology Annual Meeting, Bilbao, Spain, September 2002     

Liddle’s syndrome: a 14-year follow-up of the youngest diagnosed case

The 14-year follow-up of a female patient with Liddle’s syndrome (LS), a rare disease characterized by hypertension, hypokalemic alkalosis, and negligible aldosterone secretion due to renin suppression, is described. The disease was diagnosed at the age of 10 months (youngest identification). The patient was repeatedly investigated during follow-up for plasma renin activity (PRA), plasma aldosterone concentration (PA), serum sodium and potassium (K) concentration, blood pressure (BP), somatic anthropometry, and mental development. Noteworthy results included: persistent low circulating K, PRA, and PA and high BP, coinciding with unauthorized withdrawal of the triamterene therapy. These findings are in keeping with the hypothesis that LS results from a pathogenetic disorder which is not correctable with age. The triamterene therapy was effective in correcting the endocrine and metabolic disorders as well as arterial hypertension, but did not prevent a deficit in mental and physical development. However, the information derived from this study allows further clarification of the clinical picture of the disease. Received May 3, 1994; received in revised form and accepted February 23, 1996     

A German family with glucocorticoid-remediable aldosteronism.

BACKGROUND: The prevalence of primary hyperaldosteronism (PHA) in the hypertensive population has increased in recent years. Glucocorticoid-remediable aldosteronism (GRA) is a rare monogenic form of PHA. Here we report a German family with GRA. Since the phenotype of GRA varies widely, we asked whether recommended algorithms for PHA diagnosis distinguish GRA from other forms of PHA. METHODS: Plasma aldosterone (pg/ml) and renin (pg/ml) levels were determined in three hypertensive family members with GRA before and after sodium loading with 2 l of saline (0.9%), during posture and after 1 week of 2 mg dexamethasone daily. 24 h blood pressure and urinary excretion of aldosterone, cortisol precursors and metabolites were measured before and after dexamethasone. Southern blot hybridization and long-range PCR were performed to identify the chimeric gene. RESULTS: All three affected patients had normal potassium levels but markedly increased aldosterone/renin ratios of 472, 213 and >322 (normal range<50) indicating PHA. Sodium loading failed to lower plasma aldosterone below the threshold of 50 pg/ml in all patients. During posture, aldosterone increased in one but decreased in both other GRA patients. Elevated 18-hydroxycortisol, free aldosterone and its main metabolite aldosterone-18-glucuronid and tetrahydroaldosterone returned to normal range after 1 week dexamethasone in all patients, but blood pressure was reduced only in one patient. The chimeric gene was identified in affected family members by Southern blot and PCR. CONCLUSIONS: The aldosterone/renin ratio is a valid screening and sodium loading a valid confirmation test in GRA. Determination of elevated urinary excretion of specific aldosterone metabolites and identification of the chimeric gene are mandatory since a lacking blood pressure response to dexamethasone can be misleading.     

Urinary kallikrein excretion in patients with primary aldosteronism: differentiation of adrenal adenoma from idiopathic adrenal hyperplasia

Following 7 days on a low sodium diet, a regular sodium diet or a high sodium diet each, urine samples were collected from 37 subjects in the final days of each sodium treatment. Urinary kallikrein excretion was determined in 9 patients with primary aldosteronism, 15 normal subjects and 13 patients with essential hypertension. Urinary aldosterone excretion, plasma renin activity (PRA), urinary sodium excretion, urinary potassium excretion and p-aminohippuric acid clearance were also determined on the same days. Levels of urinary kallikrein excretion in patients with primary aldosteronism due to aldosterone-producing adenoma (APA) were greater (p less than 0.05 to p less than 0.001) than those in patients with primary aldosteronism due to idiopathic adrenal hyperplasia (IHA) under any sodium diet. Other examined variables were of limited value in differentiating patients with APA from those with IHA. Urinary kallikrein excretion, urinary excretion of electrolyte, urinary aldosterone excretion, PRA and PAH clearance were similar in normal subjects and patients with essential hypertension. It appears reasonable to conclude from these data that urinary kallikrein does not play an important role in the pathogenesis of essential hypertension, and elevated urinary kallikrein excretion in patients with primary aldosteronism due to APA can be used for biochemical differentiation from those with IHA.     

A pathophysiologic study of the hypertension associated with burn injury in children.

Measurements of cardiac output, blood volume, plasma renin activity (PRA), serum aldosterone, plasma and urinary catecholamine levels, serum and urinary electrolyte levels, and of transfusion and fluid therapy have been made in eight hypertensive and seven normotensive burned children. Studies were conducted during the acute phase of burn injury when hypertension was first diagnosed and were repeated just before discharge from the hospital. Hypertensive patients perfused at an inappropriately high total peripheral resistance and hypervolemia was demonstrated in the hypertensive patients. No differences could be demonstrated between hypertensive or normotensive patients in PRA, aldosterone, catecholamine, or electrolyte levels. These data indicate that both the hypervolemia and the vasoconstrictor activity of PRA and/or catecholamines are present when hypertension develops in these patients. These data suggest that the renin-angiotension-aldosterone system is directly stimulated as part of the neuroendocrine response to trauma.     

Role of renal prostaglandin E2 in chronic renal disease hypertension

The role played by renal prostaglandin E2 in the maintenance of hypertension in chronic renal disease has been investigated through studying the response of body weight, blood pressure, glomerular filtration rate (GFR), 24-hour natriuresis, plasma renin activity (PRA), plasma aldosterone and urinary PGE2 excretion to the administration of indomethacin (2mg/kg daily, during 3 days). A group of 37 patients diagnosed as having chronic renal parenchymatous disease with creatinine clearance above 25 ml/min was included in the study. 21 of them were hypertensive (BP greater than 160/95). 27 normotensive volunteers were also studied and considered as the control group. The initial study disclosed similar levels of PGE2, PRA and plasma aldosterone in volunteers, normotensive patients and hypertensive patients, although the sodium intake was lower in the last two groups. A positive correlation between PRA and urinary PGE2 was found both in normotensive (r = 0.507, p less than 0.01) and in hypertensive patients (r = 0.609, p less than 0.01). The administration of indomethacin induced a diminution of PRA, plasma aldosterone and urinary PGE2 levels together with an increase in diastolic blood pressure (p less than 0.05-0.01) in both volunteers and patients. The remaining parameters measured did not change in volunteers or in normotensive patients. On the contrary, in hypertensive patients, during indomethacin administration, lower values of creatinine clearance (p less than 0.005) and 24-hour natriuresis (p less than 0.05) together with an increase in body weight (p less than 0.01) were observed. These results point to the existence of a protective role of renal prostaglandin E2 upon renal function when hypertension appears in the course of chronic renal parenchymatous disease.     

Renovascular hypertension associated with neurofibromatosis: two cases and review of the literature

The authors report two cases of renovascular hypertension associated with neurofibromatosis. A 19-year-old woman was admitted to our hospital with a complaint of abdominal pain and blood pressure of 180/120 mmHg. Examination revealed café-au-lait spots over her chest and extremities. Peripheral plasma renin activity (PRA) under basal conditions was 2.8 ng/ml/h and increased to 12.6 ng/ml/h after administration of 50 mg captopril. Plasma and urinary catecholamines were normal. Selective renal angiography showed left aneurysmal dilatation of the segmentary branch and right renal artery stenosis with multiple aneurysmal affecting different branches. Blood pressure was controlled by multiple drugs, including beta-blockers and angiotensin-converting enzyme inhibitor. Another patient, a 20-year-old woman, was admitted because of severe arterial hypertension, numerous café-au-lait spots, scoliosis, and mass over the right arm. PRA from the right renal vein was extremely elevated, and selective angiography demonstrated bilateral renal artery stenosis. Aortorenal bypass was performed successfully.     

The dopaminuric response to high salt diet in insulin-dependent diabetes mellitus and in family history of hypertension

Alterations in the renal dopamine [DA] system have been suggested to contribute to the development of hypertension and diabetic nephropathy. To identify early abnormalities in renal handling of DA and sodium we challenged 16 normotensive patients with uncomplicated insulin-dependent diabetes (IDDM), 18 normotensive non-diabetic subjects with familial borderline hypertension, and 16 healthy controls, 14 – 29 years old, with a high-sodium diet (HSD). Systolic blood pressure was slightly higher in subjects with familial borderline hypertension than in the other groups on a normal sodium diet (NSD) (P<0.05). Blood pressure and 24-h urinary measurements were performed on a NSD and after 3 days on a HSD. Twenty-four-hour urinary DA excretion was similar in all groups on NSD. A significant rise in DA excretion was noted after HSD in control subjects (P<0.01), but not in subjects with a family history of hypertension or with IDDM. Urinary sodium excretion increased in all groups. A correlation between the change in DA and sodium/creatinine ratio after HSD was seen in healthy controls (r = 0.57, P = 0.02) but not in those with familial borderline hypertension (r = 0.18, P = 0.47) or with IDDM (r = 0.40, P = 0.15). A rise in systolic (but not diastolic) pressure was noted only in the IDDM group after HSD (P = 0.02). In conclusion, an impairment in the renal DA and sodium system can be detected early in IDDM and in individuals with familial hypertension. We speculate that this impairment may contribute to the development of hypertension and microvascular disease in both conditions. Received January 26, 1996; received in revised form June 3, 1996; accepted September 20, 1996     

Sodium, renin, aldosterone, catecholamines, and blood pressure in diabetes mellitus

Interrelations among plasma renin activity (PRA), aldosterone and cortisole levels, 0lood volume, exchangeable sodium, urinary catecholamines, and blood pressure were studied in 35 normal subjects and 60 age-matched non-azotemic patients with diabetes mellitus (60% with hypertension, 15% with orthostatic hypotension). Basal PRA, plasma aldosterone, cortisol, blood volume, plasma potassium, and urinary electrolytes were comparable in diabetic and normal subjects. Diabetic patients, however, had a 10% increase in body sodium (P less than 0.01), and 8% of them showed normal postural PRA responses and subnormal aldosterone responses; 22% had subnormal PRA and normal aldosterone responses, and 17% had subnormal responses of PRA and aldosterone. Non-PRA-related aldosterone responses could not be explained by ACTH or electrolytes. Orthostatic decreases in blood pressure correlated (P less than 0.01) with both catecholamine excretion and basal PRA. This suggests that in diabetes mellitus, body sodium is increased. Basal PRA and plasma aldosterone are usually normal, but their postural responses are frequently impaired. Absent aldosterone responses, despite normal PRA responsiveness, may reflect an adrenal abnormality or an ineffective form of renin. Marked postural aldosterone stimulation, unrelated to PRA, ACTH, or electrolytes, points to a potent unknown factor in aldosterone control. Low levels of free peripheral catecholamines and PRA may be complementary factors contributing to postural hypotension.     

Screening of Elderly for Chronic Kidney Disease

Background and Aims: The frequency of chronic kidney disease (CKD) markers was assessed in two groups of patients over 60 years - one without and the other with hypertension. Methods: The cross-sectional study involved 585 asymptomatic elderly patients (227 males), 93 without and 492 with hypertension. Data on patients were obtained by interview, analysis of medical records and physical examinations. Serum and urine creatinine, proteinuria, microalbuminuria (MAU, turbidimetry), and urinary sediment were analyzed. Results: Among the 585 patients, there were 54.5% with a positive family history for hypertension and 14% for kidney diseases. MAU was significantly more frequent (30 vs. 11%) and the mean estimated glomerular filtration rate (eGFR) higher (71 ± 14 vs. 64 ± 14 ml/min/1.73 m) in patients without hypertension than in those with hypertension. The majority of patients with stage 3 CKD had eGFR >45 ml/min/1.73 m(2) with normal urinary findings. Multivariate logistic regression analysis found age and treatment with angiotensin-converting enzyme inhibitors to be associated with reduced eGFR, MAU and proteinuria. In addition, smoking was associated with eGFR, but a family history for kidney disease and belonging to the group without hypertension were associated with MAU. Conclusion: The high prevalence of markers for CKD in symptomless elderly without hypertension confirmed that the elderly, as a high-risk population, should be screened based on increased age alone.     

Stimulatory effect of insulin on tubular sodium reabsorption in normotensive subjects with a positive family history of hypertension

BACKGROUND: Insulin resistance and hyperinsulinaemia has been suggestedas a pathogenetic mechanism in hypertension. METHODS: In this investigation the renal response to insulin was studiedin normotensive subjects with a positive family history of hypertensionin two generations (n = 14), in one weight-matched (n = 11)and one lean (n = 13) control group. During hyperinsulinaemia(euglycaemic hyperinsulinaemic clamp technique) we determinedrenal haemodynamics (clearances of ⁵¹Cr-EDTA and PAH) and urinarysodium excretion. Lithium clearance was used to estimate thesegmental tubular reabsorption of sodium. RESULTS: In subjects with a positive family history of hypertension,hyperinsulinaemia did not influence renal plasma flow (RPF)or glomerular filtration rate (GFR) but urinary sodium excretiondecreased by 50%. Estimated proximal tubular sodium reabsorptionwas unaffected by insulin while estimated distal fractionalsodium reabsorption increased, P<0.01. At the end of theclamp a low-dose infusion of angiotensin II (0.1 ng/kg per min)was superimposed. GFR and RPF then decreased significantly concomitantwith urinary excretion of sodium. In control subjects hyperinsulinaemia caused an unchanged GFRin both groups, increased RPF in the lean control group and15–25% reduction in sodium excretion. No alteration wasseen in estimated proximal tubular sodium reabsorption, butestimated distal tubular sodium reabsorption increased (P<0.05)in the lean control group. Angiotensin II elicited a furtherincrease in distal fractional tubular sodium reabsorption inboth control groups (P<0.05). CONCLUSIONS: In normotensive subjects with a positive family history of hypertension,in contrast to control subjects without such history, hyperinsulinaemiacaused a marked decrease in urinary sodium excretion in presenceof unchanged RPF and GFR indicating a renal tubular effect ofinsulin located at a distal site of the renal tubules. AngiotensinII caused further sodium retention, probably due to an effecton renal haemodynamics.     

Body mass index in primary and secondary pediatric hypertension

The objectives of this study were (1) to determine the relationship of body mass index (BMI) to primary or secondary hypertension in children and adolescents and (2) to assess BMI at the age of onset of hypertension in children and adolescents. Patient demographics, BMI, family history, presentation of disease, etiology of hypertension, medication, laboratory data, and findings from other procedures were recorded for all patients with hypertension followed in the Pediatric Nephrology Clinic at Childrens Hospital, Columbus, Ohio, over a 4-year period. In total, 314 patients were studied: 218 with primary hypertension and 96 with secondary hypertension. Our patient population (166 males, 148 females) was diverse in age (13±6.3 years) and ethnicity (237 Caucasians, 54 African-Americans, 23 other). BMI was greater in patients with primary (27.5±9.2 kg/m²) versus secondary (23.9±9.3 kg/m²) hypertension (P =0.002). Children with primary hypertension with an increased BMI presented at an earlier age than children with secondary hypertension and an increased BMI. The age of onset (10.5±2.6 years) in primary hypertension was related to increased BMI ( r =0.12, P =0.001); however, there was no relationship between BMI and age of onset of secondary hypertension (P =0.21). Children whose family members had essential hypertension had increased BMI compared with children without a family history of essential hypertension. Based on the logistic regression model constructed from our data, the likelihood of primary versus secondary hypertension was influenced by the presence of family history of hypertension independent of presence of obesity in the child. In conclusion, increased BMI is more common in children with primary than secondary hypertension; earlier onset of primary hypertension in the pediatric population was associated with increased BMI; the assessment of BMI is important in the evaluation of secondary as well as primary hypertension; the role of obesity in the development of secondary as well as primary hypertension in children merits further study.     

Significance of renal dopamine on pathogenesis of essential hypertension

In order to clarify the role of renal dopaminergic activity in renal sodium-water metabolism, the effects of oral administration of L-DOPA (400 mg), were studied on blood pressure (BP), plasma renin activity (PRA), plasma aldosterone concentration (PAC), urinary volume (UV), urinary excretion of sodium and lithium (UNa and ULi) in 11 normal subjects (N) and 32 patients with essential hypertension (EH). EH were divided into the salt sensitive (SS) and non salt-sensitive (NSS) groups by response of mean blood pressure (10% increase) after administration of NaCl. The change of UNa, PRA, and PAC after administration of NaCl were lower in SS than in NSS. After administration of L-DOPA, BP falled and UV, UNa, FENa, FELi and Ccr increased in both N and EH. The change of these factors were greater in SS as compared with those in NSS. These results suggest that in SS patients the suppression of water-sodium handling in the kidney might be due to depression of renal dopaminergic activity. Renal dopaminergic activity may play an important role in the pathogenesis of EH.     

Effect of L-arginine infusion in normotensive subjects with and without a family history of hypertension

BACKGROUND: Experimental studies have shown that nitric oxide (NO) generation in the kidney from L-arginine participates in the regulation of renal function. Our purpose was to study the effect of infusion of L-arginine (1, 5, and 10 mg/kg/min) on blood pressure (BP), renal hemodynamics, and urinary excretion of sodium and albumin in normotensive subjects with a family history of either severe hypertension (FHSH, N = 17) or mild hypertension (FHMH, N = 20) and in control subjects (N = 18) without a hereditary predisposition for hypertension. METHODS: The glomerular filtration rate (GFR) and renal plasma flow (RPF) were measured by renal clearances of Cr51 ethylenediaminetetraacetic acid and paramino-hippurate. Renal tubular reabsorption of sodium was estimated by lithium clearance. To evaluate the effect of L-arginine infusion on the L-arginine/NO pathway, we measured the NO-metabolite nitrate in plasma, and urinary excretion of cGMP, the second messenger of NO. The derivative at an L-arginine dose of 7.5 mg/kg/min was used as a measure of sensitivity to L-arginine. RESULTS: There was no difference in baseline systolic BP between the groups, but diastolic BP was significantly higher in FHSH compared with control subjects (P < 0.05). L-arginine caused a significant increase in urine flow, urinary excretion of albumin and sodium, and lithium clearance in all groups. FHSH showed a significantly decreased sensitivity to L-arginine with respect to urine flow rate (P = 0029) compared with FHMH and control subjects. L-arginine caused a significant decrease in the GFR in FHSH (P < 0.02) and control subjects (P < 0.001), but in FHMH, the decrease did not reach statistical significance (P = 0.097). There was no difference in sensitivity to L-arginine with respect to BP, RPF, or GFR between the three groups. In all patients, there was a significant positive relationship between Delta urine flow rate or Delta urinary sodium excretion and Delta GFR during infusion of L-arginine (P = 0.003 and P = 0.03, respectively). Plasma nitrate and urinary cGMP decreased in all groups during the L-arginine infusion. CONCLUSION: L-Arginine infusion in normotensive subjects caused an enhanced urine flow rate and urinary sodium and albumin excretion and a slight reduction in GFR. The effect of L-arginine on the urine flow rate was significantly less pronounced in subjects with a family history of severe hypertension, which may indicate a tubular disturbance in hypertension.