Factors associated with glomerular hyperfiltration in the early stage of hypertension

BackgroundGlomerular hyperfiltration predicts development of nephropathy in hypertension but the factors responsible for increased glomerular filtration rate (GFR) are not well known. Aim of this study was to examine which clinical variables influence GFR in the early stage of hypertension.MethodsParticipants were 1,106 young-to-middle-age hypertensive adults with creatinine clearance >60 ml/min/1.73 m(2). Clinic and ambulatory blood pressures (BPs) were measured and the difference between clinic and 24-h systolic BP was defined as the white-coat effect (WCE). In 606 participants, 24-h urinary epinephrine and norepinephrine were also measured. Glomerular hyperfiltration, defined as a GFR ≥150 ml/min/1.73 m(2), was present in 201 subjects.ResultsPatients' mean age was 33.1 ± 8.5 years and office BP was 146 ± 10.5/94 ± 5.0 mm Hg. In multivariable linear regression, significant predictors of GFR were younger age (P < 0.0001), male gender (P < 0.0001), 24-h systolic BP (P = 0.0001), body mass (P < 0.0001), WCE (P = 0.02), log-epinephrine (P = 0.01), and coffee use (P < 0.01). In a logistic model, independent predictors of glomerular hyperfiltration were obesity (odds ratio, 95% confidence interval = 6.1, 3.8-9.8), male gender (2.9, 1.8-4.9), age <33 years (2.1, 1.5-3.1), ambulatory hypertension (2.0, 1.4-3.0), WCE >15 mm Hg (1.6, 1.1-2.3), heavy coffee use (2.0, 1.1-3.8), and epinephrine >25 mcg/24 h (1.9, 1.2-3.1).ConclusionsThe novel finding of this study is that hyper-reactivity to stress, as determined by urinary epinephrine level and WCE, and coffee use contribute to determining glomerular hyperfiltration in the early stage of hypertension. Our data may help to identify a subset of patients with glomerular hyperfiltration, who may be at increased risk of chronic kidney disease and may benefit from antihypertensive treatment.American Journal of Hypertension 2012; doi:10.1038/ajh.2012.73.     

Glomerular hyperfiltration in microalbuminuric NIDDM patients

Summary Glomerular hyperfiltration and microalbuminuria are both regarded as risk factors for the development of diabetic nephropathy in insulin-dependent diabetic patients. Information on glomerular hyperfiltration is scarse in microalbuminuric non-insulin-dependent diabetic (NIDDM) patients. Therefore, we performed a cross-sectional study of glomerular filtration rate (single i. v. bolus injection of ⁵¹Cr-EDTA, plasma clearance for 4 h) in 158 microalbuminuric NIDDM patients compared to 39 normoalbuminuric NIDDM patients and 20 non-diabetic control subjects. The groups were well-matched with regard to sex, age and body mass index. The uncorrected (ml/min) and the adjusted (ml · min^–1· 1.73 m^–2) glomerular filtration rate were both clearly elevated in the microalbuminuric patients: 139 ± 29 and 117 ± 24 as compared to 115 ± 19 and 99 ± 15; 111 ± 23 and 98 ± 21 in normoalbuminuric NIDDM patients and control subjects, respectively (p < 0.001). The glomerular filtration rate (ml · min^–1· 1.73 m^–2) in NIDDM patients who had never received antihypertensive treatment was also clearly elevated in the microalbuminuric patients (n = 96): 119 ± 22 as compared to 100 ± 14 and 98 ± 21 in normoalbuminuric NIDDM patients (n = 27) and control subjects (n = 20), respectively (p < 0.001). Glomerular hyperfiltration (elevation above mean glomerular filtration rate plus 2 SD in normoalbuminuric NIDDM patients) was demonstrated in 37 (95 % confidence interval 30–45)% of the microalbuminuric patients. Multiple regression analysis revealed that HbA_{1 c}, 24-h urinary sodium excretion, age and known duration of diabetes were correlated with glomerular filtration rate in microalbuminuric NIDDM patients (r ² = 0.21, p < 0.01). Our cross-sectional study indicates that NIDDM patients at high risk of developing diabetic nephropathy are also characterized by an additional putative risk factor for progression, glomerular hyperfiltration. [Diabetologia (1996) 39: 1584–1589]     

Nitric oxide system is involved in glomerular hyperfiltration in Japanese normo- and micro-albuminuric patients with type 2 diabetes

Glomerular hyperfiltration plays a pathogenic role in the early stages of diabetic nephropathy. Experimental studies in laboratory animals suggest that nitric oxide (NO) might be involved in the pathogenesis of glomerular hyperfiltration. We performed a cross-sectional study to determine the relationship between diabetic glomerular hyperfiltration and the NO system. Normoalbuminuric (n=41), microalbuminuric (n=25), and macroalbuminuric (n=16) patients with type 2 diabetes were recruited in this study and compared with age-matched 84 non-diabetic control subjects. Creatinine clearance and urinary NO(2)(-)/NO(3)(-) excretion (urinary NOx) were measured, and the expression of endothelial cell nitric oxide synthase (ecNOS) was evaluated in human renal tissues. Glomerular hyperfiltration was present in 19 (37.5%) and nine (36.6%) of normoalbuminuric and microalbuminuric type 2 diabetic patients, respectively. The urinary NOx was significantly higher in normoalbuminuric patients compared with normal subjects. Creatinine clearance correlated significantly with urinary NOx in normoalbuminuric and microalbuminuric patients. Immunohistochemical staining intensities for ecNOS were significantly increased in glomerular endothelial cells of microalbuminuric type 2 diabetic patients as compared with the control subjects. These results suggest that NO may contribute to the pathogenesis of glomerular hyperfiltration in Japanese type 2 diabetic patients.     

Arterial hypertension and diabetic nephropathy]

A high incidence of renal lesions is observed in patients with insulin-dependent diabetes. In the early stages of the disease glomerular capillary hemodynamics is altered with, in particular, glomerular hyperfiltration related to several factors: enhanced glomerular capillary flow rate, capillary hypertension and increased filtration area. These hemodynamic changes could affect development of the glomerular microangiopathy: the final outcome of this is the glomerulosclerosis associated with a progressively worsening and ineluctable chronic renal insufficiency. Hypertension, frequent in the early stages, is practically constant when the neuropathy stage has been reached; it is well established that hypertension accelerates the development of glomerular lesions and the progression of the renal impairment. Experimental and clinical studies have clearly demonstrated that antihypertensive treatment slows down the degradation of renal function. All antihypertensive drugs appear to be effective, but converting enzyme inhibitors, by their effects on renal hemodynamics, could play a particular role in the prophylactic treatment of diabetic nephropathy. Determination of urinary excretion of albumin (microalbuminuria), the global evidence of the onset of a nephropathy is useful for the follow up of the renal disease, allows follow up of the renal lesion and evaluation of the efficacy of treatment.     

Glomerular hyperfiltration in type I, type II, and secondary diabetes.

Glomerular hyperfiltration, a risk factor for diabetic nephropathy, has been reported in type I insulin-dependent diabetics, but it is not clear if it occurs in other types of diabetes. To ascertain the prevalence of glomerular hyperfiltration in various types of diabetes, we measured glomerular filtration rate (GFR) in 158 diabetics (91 type I, 36 type II without insulin treatment, 20 type II with insulin treatment, and 11 subjects with diabetes secondary to chronic pancreatitis), and classified them as hyper-, normo-, or hypofiltration according to values measured in 36 age-match controls. After elimination of subjects with overt renal disease or hypertension, glomerular hyperfiltration was detected in 35% of the type I diabetics, 32% of the type II diabetics without insulin treatment, one subject with chronic pancreatitis, and one type II diabetics with insulin treatment. Glomerular hyperfiltration was associated with high blood glucose in type I, insulin-dependent diabetics, and with a high apolipoprotein B/A1 ratio in type II, non-insulin-dependent diabetics without insulin treatment. In all subjects with glomerular hyperfiltration, GFR values and urinary albumin excretion were positively related (r = 0.33; n = 34; p = 0.05). Glomerular hyperfiltration is detectable among all types of diabetics.     

Microalbuminuria and oxidative stress in essential hypertension

OBJECTIVE: To assess the relationship between microalbuminuria and oxidative stress in mononuclear peripherals cells in essential hypertension. METHODS: A total of 123 hypertensive patients in absence of antihypertensive treatment were included. A 24-h ambulatory blood pressure (BP) monitoring was performed using a Spacelabs 90207 monitor, and microalbuminuria was measured in 24-h urine collections. Oxidized/reduced glutathione ratio and the content of malondialdehide and damaged base 8-oxo-2'-deoxyguanosine in genomic and mitochondrial DNA were measured in peripheral mononuclear cells. RESULTS: In the 29 (24%) microalbuminuric subjects, the amount of reduced glutathione was significantly lower and the ratio oxidized/reduced glutathione was significantly higher than in the normoalbuminuric subjects. In contrast, the simultaneous measurement of the levels of malondialdehide and 8-oxo-2'-deoxyguanosine from both genomic and mitochondrial DNA oxidation did not achieve statistical significance between the two groups. Subjects with the highest oxidized/reduced glutathione ratio tertile showed the highest urinary albumin excretion (UAE) (P = 0.04 for trend). In a stepwise multiple regression analysis, oxidized/reduced glutathione ratio was the main significant determinant of UAE accounting for the 9% of the variance when 24-h mean BP, age, sex, body mass index, glucose and total cholesterol were included in the model. CONCLUSIONS: Oxidative stress seems to be a determinant of UAE independent of BP levels even in hypertensive subjects.     

Renal effects of diltiazem in primary hypertension

Although the calcium channel blocker diltiazem has been shown to be an effective antihypertensive agent, its effect on renal function, salt and water excretion, and body fluid composition has not been well characterized in patients with primary hypertension. Therefore, these parameters were prospectively studied in 18 subjects with primary hypertension after placebo and 8 weeks of diltiazem monotherapy. Diltiazem monotherapy was confirmed to be an effective antihypertensive agent. Although mean arterial pressure was reduced from 121 to 108 mm Hg, diltiazem had no overall effect on glomerular filtration rate, renal plasma blood flow, salt and water excretion, or body fluid composition. Renal vascular resistance, however, was decreased. In subjects with pretreatment glomerular filtration rates of 80 ml/min/1.73 m2 or less, diltiazem therapy was associated with marked improvement in glomerular filtration rate (48%) and effective renal plasma flow (36%). Since the filtration fraction was unchanged, changes in glomerular filtration rate may have been related to the attenuated intrarenal effects of angiotensin II or norepinephrine, or both.     

Efficacy of antihypertensive treatment with indapamide in patients with noninsulin-dependent diabetes and persistent microalbuminuria

In patients with insulin-dependent diabetes, antihypertensive treatment has a beneficial effect on the rate of progression toward uremia of overt diabetic nephropathy (albumin excretion rate [AER] greater than 300 mg/24 hour). The influence of hypertension on the progression of "incipient" nephropathy (AER ranging between 30 and 300 mg/24 hours) is not well defined, particularly in patients with noninsulin-dependent diabetes. In this study, 21 patients with noninsulin-dependent diabetes and hypertension (11 with normoalbuminuria and 10 with microalbuminuria), who were comparable for age, duration of diabetes and hypertension, were treated with indapamide, 2.5 mg once daily, and followed up for 24 months. Blood pressure, glomerular filtration rate (GFR), albumin excretion rate and subclass 4 of urinary immunoglobulin G (IgG4) were indicated. In normoalbuminuric patients, blood pressure was significantly reduced, whereas AER, IgG4 and GFR did not show any variation throughout the study. In microalbuminuric patients, blood pressure, AER and IgG4 were significantly reduced, and GFR remained unchanged. In patients with noninsulin-dependent diabetes, antihypertensive treatment, which is begun during incipient diabetic nephropathy, may have a beneficial effect on the progression of the disease, although a long-term follow-up study is needed to confirm this.     

Plasma immunoreactive endothelin in essential hypertension

PURPOSE: Endothelin plays a role in the regulation of vascular tonus. Therefore, it has been hypothesized that increased production or release of endothelin or both may contribute to the pathogenesis of hypertension. To assess any changes in the plasma endothelin concentration in essential hypertension, plasma immunoreactive endothelin concentrations were measured in patients with essential hypertension. PATIENTS AND METHODS: We measured plasma immunoreactive endothelin concentrations in 42 subjects with essential hypertension, 12 subjects with borderline hypertension, and 25 normotensive control subjects. RESULTS: The concentrations were higher in hypertensive patients than in borderline hypertensive patients and normotensive subjects (both p less than 0.05), although values in normotensives and hypertensives overlapped. Reverse-phase high-performance liquid chromatography (HPLC) and radioimmuno-assay showed two components of plasma endothelin, one corresponding to synthetic endothelin-1 (1-21) and the other corresponding to synthetic big endothelin (human, 1-38). The HPLC profile of plasma endothelin of hypertensive patients was the same as that of normotensive subjects. Hypertensives with reduced glomerular filtration rates or increased serum creatinine levels had higher plasma endothelin concentrations than hypertensive patients as a whole (p less than 0.05). Mean blood pressure and serum creatinine levels were correlated to plasma endothelin in the hypertensives. Correlation was negative between glomerular filtration rate and the endothelin level in the hypertensives. CONCLUSION: Plasma endothelin was elevated in many hypertensive patients with severe hypertension or renal involvement. Its major components were endothelin-1 and big endothelin.     

Family history of hypertension influences left ventricular diastolic function during chronic antihypertensive therapy

BACKGROUND: Genetic factors play an important role in linking insulin resistance and hypertension, also influencing insulin sensitivity changes during antihypertensive treatment. This study was aimed to evaluate whether genetic predisposition to hypertension can also influence left ventricular (LV) changes during antihypertensive treatment. METHODS: We enrolled 36 never-treated hypertensives: 18 with both parents hypertensive (F+) and 18 with both parents normotensive (F-), matched for age, gender, and body mass index (BMI). The patients were evaluated twice, before and after 2.5 years of treatment with enalapril. At both evaluations the patients underwent: 24-h blood pressure (BP) monitoring, LV echocardiogram, and oral glucose tolerance test, with measurements of glucose and insulin levels. RESULTS: At basal evaluation the two groups were not different with regard to gender, age, BMI, 24-h BP, and fasting glucose; glucose metabolic clearance rate was significantly lower in F+. The LV mass index was similar between the groups, whereas diastolic parameters were significantly lower in F+. At second evaluation, 24-h BP and LV mass were decreased to the same extent in both groups; glucose metabolic clearance rate significantly increased in F- and remained unchanged in F+. The improvement of LV diastolic function, found in both group, was significantly greater in F-. CONCLUSIONS: Genetic predisposition to hypertension, in addition to affecting insulin sensitivity, influences LV functional changes during antihypertensive treatment. Despite a similar extent of 24-h BP and LV mass decrease, F+ patients showed no changes in insulin sensitivity and a smaller improvement in LV diastolic function than F-.     

The relationship between casual and ambulatory blood pressure in essential hypertension: the influence of work, duration of hypertension and antihypertensive treatment

Casual blood pressure (BP) and ambulatory BP (mean 24-h BP) were determined in 23 untreated patients with essential hypertension and in 11 normotensive healthy control subjects. Mean 24-h BP was significantly lower than casual BP in patients with essential hypertension, but not in control subjects. This was demonstrated in the patients who did not work during the ambulatory BP monitoring and in the patients with newly recognized hypertension, whereas no differences were revealed either in the patients who went to work or had a known duration of hypertension longer than 6 months. The size of the difference between casual BP and mean 24-h BP was unaffected by antihypertensive therapy with metoprolol and also individually reproducible. An accordance between casual and ambulatory BP measurements in evaluation of the efficacy of antihypertensive treatment was found in 75% of the patients. Casual BP and mean 24-h BP were weakly correlated both before and during antihypertensive treatment. It is concluded that the higher casual BP than ambulatory BP in essential hypertension may be a specific characteristic of the disease. Both work and known duration of hypertension longer than 6 months eliminate the difference between casual ambulatory BP in essential hypertension. Ambulatory BP monitoring seems to be superior to casual BP measurements in the evaluation of antihypertensive treatment.     

Associations of microalbuminuria and blood pressure with carotid, aortic and femoral atheromatous plaques in elderly Finns

AIMS: To evaluate the possible associations of microalbuminuria (MA) and blood pressure (BP) with the ultrasonographic manifestations of carotid, aortic and femoral atherosclerosis in 65-year-old Finns. METHODS: Ultrasonographic measurements were performed on 54 diabetic subjects, 97 subjects with impaired glucose tolerance (IGT) and 57 normoglycemic subjects (NGT). Urinary albumin and creatinine concentrations were measured from an early morning spot urine sample, and the urinary albumin-to-creatinine ratio (ACR) of > or = 2.5 mg/mmol in men and > or = 3.5 mg/mmol in women was used as a measure of MA. Hypertension was defined as either a systolic BP of > or = 160 mmHg or a diastolic BP of > or = 95 mmHg or being on antihypertensive medication. RESULTS: Eighteen subjects were microalbuminuric and 176 subjects normoalbuminuric. MA was associated with diabetes mellitus and high systolic and diastolic BP. The subjects were divided into two groups according to the median total number of carotid, aortic and femoral plaques: > or = 9 versus 0-8 plaques. A high number of plaques were associated with hypertension, male gender, smoking and MA. When the study subjects were stratified according to hypertension, it turned out that MA was associated with a high number of plaques in hypertensive, but not in nonhypertensive subjects. According to the results of logistic regression analysis with a high number of plaques as the dependent variable, the unadjusted OR for smoking was 6.0 (95% CI 2.4-15.3) in hypertensive subjects. Microalbuminuria was of borderline statistical significance (OR 4.5, 95% CI 0.9-22.9). After adjustment for systolic blood pressure and fasting glucose concentration, the OR for microalbuminuria was reduced to 3.3 (95% CI 0.6-18.4).     

Left ventricular mass and glomerular hyperfiltration in essential hypertension

OBJECTIVE: to assess the early involvement to target organs in never treated essential hypertensives (HT). METHODS: effective renal plasma flow (ERPF, 131I-Hippurate) and glomerular filtration rate (GFR, 99mTc-DTPA) were estimated in 80 mild HT. Left ventricular mass (LVM, M-mode echocardiography), sodium intake (24h UNaV) and urinary kallikrein (Kall) were also measured. Hyperfiltering patients (HF, GFR = 155 +/- 3 ml/min: 1.73 m2, n = 21) were defined by comparison with age-matched normotensive. HF patients were pair-matched for age, sex and blood pressure level with normofiltering hypertensives (NF, GFR = 112 +/- 3, n = 21). RESULTS: are expressed as mean +/- sem [table: see text] CONCLUSION: These results suggest that a high Na intake is associated with hyperfiltration and higher LVMI in subjects with never treated essential hypertension of short duration.     

Arterial hypertension in glomerulonephritis]

The duration of nephropathy, the onset of arterial hypertension (AH), a family history of AH, uric syndrome, intravenous urographic evidence, glomerular filtration rate (GFR) determined from endogenous creatinine, the cellular membranes studied in erythrocytes by ureal hemolysis, and blood levels of thiol and disulfide groups by back amperometric titration, red blood cell activity of glutathione reductase and glucoso-6-phosphate dehydrogenase were evaluated in 108 patients with essential hypertension (EH), mesangial proliferative glomerulonephritis who had elevated and normal blood pressures and 18 healthy subjects. All the patients underwent closed renal puncture biopsy. There were structural alterations in the red blood cell membranes as evidenced by examinations of glucose-6-phosphate dehydrogenase, thiol and disulfide groups in erythrocyte protein and low-weight molecular fractions in healthy subjects with a family history of AH, patients with EH, with mesangial proliferative glomerulonephritis. The abnormal uric syndrome was detected in patients with EH. Patients with AH displayed glomerular hyperfiltration and higher glomerular dimensions. Renal biopsy revealed adrenal interstitial sclerosis in patients with AH.     

Isolated office hypertension: a 3-year follow-up study

The study aimed to evaluate, over a 3-year period, the progression towards sustained hypertension and left ventricular (LV) changes in patients with isolated office (IO) hypertension (office BP>140 and/or 90 mmHg, daytime BP<130/80 mmHg). After 3 years from the basal evaluation, 38 subjects with basal normal BP and 42 subjects with basal IO hypertension underwent a second 24-h BP monitoring and echocardiography; 19 patients of the basal IO hypertension group were not revaluated because they had already developed ambulatory hypertension and were on antihypertensive treatment. At the second evaluation, the 38 normotensive subjects had unchanged BP and LV parameters; 25 IO hypertensives have developed sustained hypertension. Considering them together with the 19 patients already treated, 72% of 61 IO hypertensives developed ambulatory hypertension over a 3-year period. The patients who subsequently developed hypertension differed from the group who did not only for lower basal values of LV diastolic parameters; all the patients with basal LV hypertrophy and/or preclinical diastolic impairment subsequently developed sustained hypertension. In conclusion, IO hypertensive patients show a high rate of progression towards sustained hypertension. Basal LV hypertrophy and/or preclinical diastolic dysfunction were the only markers of a greater risk of becoming hypertensives.     

Distribution of target-organ abnormalities by race and sex in children with essential hypertension

The prevalence of left ventricular hypertrophy, glomerular hyperfiltration and retinovascular abnormalities was investigated in 43 black and 45 white children with essential hypertension. Whilst 36% of subjects had left ventricular hypertrophy, 49% had glomerular hyperfiltration and 50% had retinal abnormalities, no differences were found between blacks and whites. This pattern differs from that found in adult hypertensives.     

Contrasting renal functional reserve in very long-term Type I diabetic patients with and without nephropathy

AIMS: This study was to determine whether renal functional reserve (RFR) is present in patients who have suffered long-lasting Type I (insulin-dependent) diabetes mellitus. METHODS: Renal functional reserve was elicited by a 3-h amino acid infusion (4.5 mg x kg(-1) x min(-1)) in 10 patients with nephropathy (DN+) and 10 patients without nephropathy (DN-) who had lived with diabetes for 24 +/- 3 and 27 +/- 3 years, respectively and in 15 healthy control subjects. Renal functional reserve was calculated as the difference between amino acid-stimulated and baseline glomerular filtration rates (GFR). RESULTS: Baseline glomerular filtration rate in DN- patients (106 +/- 8) and control subjects (112 +/- 3 ml x min(-1) x (1.73m2)(-1)) was significantly higher (p < 0.01) than in DN+ patients (79 +/- 7 ml x min(-1) x (1.73m2)(-1)). Renal functional reserve was absent in DN+ patients, whereas it represented 26 +/- 4% of the baseline in DN- patients and 23 +/- 2% in control subjects. Renal vascular resistance decreased statistically significantly during amino acid infusion in DN- patients and control subjects but not in DN+ patients. CONCLUSIONS/HYPOTHESIS: These results indicate that very long-term Type I diabetic patients without diabetic nephropathy still have a normal renal functional reserve. In contrast, this reserve is suppressed in similarly long-term macroalbuminuric and hypertensive patients with overt nephropathy in spite of their remarkably maintained glomerular filtration rate. This opposite impairment supports the interpretation that glomerular hyperfiltration is a determining mechanism in human diabetic nephropathy.     

Glomerular hyperfiltration in hypertensive African Americans

The incidence of end-stage renal disease attributable to hypertension is 5-fold greater in African Americans than in whites. To determine whether glomerular hyperfiltration is an antecedent to renal failure, we compared responses of renal blood flow and glomerular filtration rate to graded infusions of norepinephrine (0. 01, 0.025, and 0.05 microg. kg(-1). min(-1) for 30 minutes each) in 29 African Americans and 33 age-matched French Canadian whites with essential hypertension. Renal blood flow and glomerular filtration rate were measured by using a constant-infusion technique of PAH and inulin, respectively. Studies were conducted on an inpatient clinical research center, and antihypertensive medications had been discontinued for at least 1 week. Based on 24-hour blood pressure monitoring, nighttime blood pressures decreased (P<0.01) in the French Canadians but not in the African Americans. Baseline renal blood flow was higher (P<0.05) in the African Americans (1310+/-127 mL. min(-1) per 1.73 m(2)) than in the French Canadians (1024+/-42 mL. min(-1) per 1.73 m(2)); baseline glomerular filtration rate was also higher (P<0.01) in the African Americans (140+/-4 versus 121+/-4 mL. min(-1) per 1.73 m(2)). In response to norepinephrine-induced blood pressure increases, renal blood flow was autoregulated and did not change in either patient group. In the African Americans, glomerular filtration rate increased (P<0.01) to 167 mL. min(-1) per 1.73 m(2) during the first norepinephrine infusion, without subsequent change. In contrast, glomerular filtration rate did not change with norepinephrine-induced increases of blood pressure in the French Canadians. In the African Americans, the elevation of baseline glomerular filtration rate, with a further increase in response to norepinephrine, may be indicative of glomerular hyperfiltration. Glomerular hyperfiltration and lack of nocturnal blood pressure decline may contribute to the higher incidence of end-stage renal disease in hypertensive African Americans.     

G-protein beta(3) subunit gene (GNB3) 825T allele is associated with enhanced renal perfusion in early hypertension

The C825T polymorphism of the gene encoding the G-protein beta(3) subunit (GNB3) is associated with increased intracellular signal transduction and arterial hypertension. The aim of the study was to investigate the impact of this polymorphism on early adaptive processes of the left ventricle and renal hemodynamic changes in young normotensive to mildly hypertensive subjects. Ninety-five white male students with normal or mildly elevated blood pressure were genotyped for the GNB3 C825T polymorphism. In each participant, 24-hour ambulatory blood pressure, left ventricular structure and function (2D-guided M-mode echocardiography), renal plasma flow (para-aminohippurate clearance), glomerular filtration rate (inulin clearance), and 24-hour urinary sodium excretion were determined. The GNB3 825T allele was not associated with casual or ambulatory blood pressure, parameters of left ventricular structure or function, glomerular filtration, or 24-hour urinary sodium excretion. However, in T:-allele carriers (CT+TT), renal plasma flow was higher than in CC subjects (CT/TT: 659+/-96 versus CC: 614+/-91 mL/min, P:=0.019). ANOVA disclosed that renal plasma flow was independently influenced by both genotype and blood pressure, with hypertensives having a higher renal plasma flow than normotensive subjects. This was the fact irrespective of the criteria used for the definition of hypertension (World Health Organization or 24-hour ambulatory blood pressure criteria). The GNB3 825T variant is associated with increased renal perfusion in this study. Because early renal hemodynamic changes play a pivotal role in the pathogenesis of essential hypertension, our data suggest a relevance of increased G-protein activation in the pathogenesis of hypertension.     

Glomerular hypertension and hyperfiltration in adrenocorticotrophin-induced hypertension in rats: the role of nitric oxide

OBJECTIVE: To determine the effects on pre- and post-glomerular vascular resistance of adrenocorticotrophin (ACTH)-induced hypertension in rats, before and after blockade of nitric oxide formation. DESIGN: Four groups of Sprague-Dawley rats were studied. Measurements were made in ACTH- (Synacthen Depot, 0.25 mg/kg twice daily for 8 days) and sham-treated anaesthetized rats, before and after either Nomega-nitro-L-arginine (L-NNA, 6 mg/kg) or vehicle. METHODS: Whole-kidney and single-nephron haemodynamics and function were measured. Glomerular capillary pressure was estimated from tubular stop-flow pressure measurements. RESULTS: Blood pressure (P < 0.001), renal blood flow (RBF, P < 0.05) and glomerular filtration rate (P < 0.01) were increased following ACTH treatment compared with sham. There were no differences in either total renal, or pre- or post-glomerular vascular resistances, but stop-flow-estimated glomerular capillary pressure was elevated (P < 0.001) as was single-nephron glomerular filtration rate (SNGFR) (P < 0.001) and single-nephron blood flow (P < 0.01 ) in the ACTH- compared to the sham-treated rats. L-NNA treatment increased blood pressure by a similar extent in both ACTH- and sham-treated rats, but reduced RBF (P < 0.05) and glomerular filtration rate (GFR) (P < 0.05) more in the ACTH group; similar changes were seen in single-nephron values. L-NNA increased pre- and post-glomerular resistances to a greater extent in the ACTH group. CONCLUSIONS: ACTH-induced hypertension produced glomerular hypertension and hyperfiltration, which may be due to nitric oxide-related vasodilatation of the renal vasculature.