Impaired stress-induced pressure natriuresis increases cardiovascularload in African American youths

BackgroundWe hypothesized that impaired stress-induced pressure natriuresis increases blood pressure (BP) load.MethodsThe 118 African American youths were brought into similar levels of sodium balance. The protocol consisted of a 2-h baseline period, a 1-h stress period (competitive video games), and a 2-h recovery period.Results:Normal pressure natriuresis (n = 80) resulted from a resistance-mediated (r = 0.23; P < .03) increase in BP (P < .001). In contrast, impaired pressure natriuresis (n = 38), leading to an extended period of elevated BP (P < .05), resulted from a volume-mediated (r = 0.55; P < .002) increase in BP (P < .001).Conclusions:Impaired stress-induced pressure natriuresis may contribute to the development of essential hypertension, particularly in African Americans.     

Effect of amlodipine on hemodynamic and endocrine responses to mental stress

Little is known about the effects of antihypertensive drugs on hemodynamic responses to mental stress. We studied 24 patients with mild-to-moderate hypertension in a double-blind random-sequence crossover study comparing placebo with amlodipine titrated up from 5 to 10 mg daily. After 1 month of treatment, the subjects performed 20 min of a frustrating cognitive task. At baseline before task, amlodipine significantly reduced systolic pressure (128.9 ± 8.2 mm Hg v 140.3 ± 10.7 mm Hg, P < .001), diastolic pressure (81.7 ± 7.7 mm Hg v 90 ± 7.5 mm Hg, P < .001), and total peripheral resistance (37.5 ± 15 v 45.6 ± 23.7 mm Hg/L/min, P < .05), while elevating baseline norepinephrine levels (2286 ± 731 pmol/L v 1788 ± 546 pmol/L, P < .001).Blood pressure during the stress task was significantly less with amlodipine than with placebo (systolic 142.3 ± 12.3 mm Hg v 150.9 ± 14.6 mm Hg, P < .001; diastolic 87.9 ± 8.4 mm Hg v 97.7 ± 9.3 mm Hg, P < .001), whereas norepinephrine was significantly higher (2754 ± 1007 pmol/L v 1970 ± 740 pmol/L, P < .001).There were no significant differences in cardiac output, plasma lipids or lipoproteins, or markers of platelet activation. Heart rate increased significantly during stress, but there was no significant difference between amlodipine and placebo either at baseline or during stress. Our conclusion is that amlodipine reduces blood pressure at baseline and during mental stress, but raises basal and stress-related plasma catecholamines. This finding may have implications for the recent controversy over the safety of calcium channel antagonists, and suggests the potential relevance of combining amlodipine with adrenergic blockers.     

Endothelin-1 and -3 plasma concentrations in patients with cirrhosis: Role of splanchnic and renal passage and liver function

Increased as well as decreased plasma concentrations of the endothelins, endogenous vasoactive peptides, have been reported in cirrhosis. This might be caused by alterations of hepatic or renal clearance or release. Therefore, the aim of the current study was to investigate the influence of splanchnic and renal passage and of liver function on plasma concentrations of endothelin-1 (ET-1) and endothelin-3 (ET-3) in patients with cirrhosis compared with controls. Eighteen patients with cirrhosis and 8 normotensive controls of similar age were investigated. Arterial and venous plasma samples were obtained simultaneously, and ET-1 and ET-3 concentrations were determined in extracted plasma by two separate radioimmunoassays. Arterial as well as hepatic and renal venous concentrations of ET-1 in cirrhosis (17.8 ± 0.8 pg/mL, 19.1 ± 0.9 pg/mL, and 16.8 ± 0.8 pg/mL) were significantly (P < .001) higher than in controls (9.2 ± 1.7 pg/mL, 9.0 ± 2.0 pg/mL, and 8.4 ± 1.9 pg/mL, respectively). The same held true for the corresponding ET-3 plasma concentrations in cirrhosis (19.3 ± 1.6 pg/mL, 20.5 ± 1.5 pg/mL, and 18.4 ± 1.5 pg/mL, respectively) compared with controls (11.1 ± 1.8 pg/mL, 11.3 ± 1.5 pg/mL, and 10.1 ± 1.7 pg/mL, respectively; P < .01). There was a significant (P < .05) renal net extraction of ET-1 and ET-3 in cirrhosis. In contrast, a significant (P < .05) net release of ET-1 and ET-3 (2.40 ± 0.80 ng/min and 1.75 ± 1.16 ng/ min) during splanchnic passage was observed in cirrhosis, but not in controls (−0.24 ± 0.51 ng/min, and −0.46 ± 0.64 ng/min). Plasma concentrations of ET-3 in cirrhosis were correlated to the Child-Turcotte score (r = .66, P < .01) and inversely to the functional liver cell mass, determined by the galactose elimination capacity (r = −.72, P < .01). Hepatic venous ET-1 concentrations correlated to the hepatic blood flow assessed by the indocyanine green clearance (r = .48; P < .05). Net splanchnic release may contribute to elevated ET-1 and ET-3 plasma concentrations in patients with cirrhosis. Splanchnic ET-1 and ET-3 handling in cirrhosis may be influenced by different mechanisms.     

Role of plasma and urinary endothelin-1 in early diabetic and hypertensive nephropathy

To evaluate the role of circulating and renal endothelin-1 (ET-1) in early diabetic nephropathy, plasma ET-1 levels and urinary ET-1 excretion were evaluated in lean, normotensive patients affected by non–insulin-dependent diabetes (NIDDM) either with (n = 9, NIDDM+) or without microalbuminuria (n = 18, NIDDM−); in never-treated, lean, essential hypertensive patients with (n = 12, EH+) or without microalbuminuria (n = 10, EH−); and in healthy volunteers (n = 12). Results showed higher plasma ET-1 levels in NIDDM+ (1.97 ± 0.58 pg/mL) than in NIDDM− (1.59 ± 0.14 pg/mL, P = .013), EH+ (1.40 ± 0.21 pg/mL, P = .005), EH− (0.91 ± 0.19 pg/mL, P < .0001), and controls (0.60 ± 0.10 pg/mL, P < .0001). The circulating ET-1 concentration was also higher in EH+ than EH− and controls (P < .0001).Urinary ET-1 excretion did not differ (P = .387, NS) between NIDDM+ (48.5 ± 20.1 pg/min) and NIDDM− (40.9 ± 21.6 pg/min), but was significantly reduced (P < .0001) in both groups compared with controls (70.0 ± 15.5 pg/min). Similar findings were observed in hypertensive subgroups. No correlations were found between urinary ET-1 and other variables, including plasma ET-1 levels, in all groups.In conclusion, NIDDM+ is accompanied by a significant increase in plasma ET-1 levels. A significant elevation of circulating ET-1 concentration was evident also in NIDDM−, suggesting that early abnormalities of ET-1 production might precede the microalbuminuric phase of diabetes-related renal damage.     

Circadian rhythm of urinary endothelin-1 excretion in mild hypertensive patients

Endothelin-1 (ET-1) is a potent vasoconstrictive peptide with diverse physiologic actions and has been considered to be involved in the pathogenesis of hypertension. We sought to investigate the role of renal synthesis of ET-1 in the regulation of daily sodium homeostasis and the possible contribution of renal synthesized ET-1 in the pathogenesis of essential hypertension (EHT). Urinary ET-1–like immunoreactivity (ET-1-Ll) was measured by a radioimmunoassay after extraction in 23 EHT patients without detectable target organ damage, and in 11 normotensive controls. All study subjects received a controlled diet during an 8-day study period. Urinary and blood samples were collected by four sampling periods/day from the 4th to 6th days, and on the 7th day, study subjects were given an intravenous infusion of 1250 mL normal saline over 2 h. In the basal state, the urinary sodium and ET-1-Ll excretions showed diurnal patterns in both the normal and hypertensive groups, and urinary ET-1-Ll excretion rate correlated well with urinary sodium excretion rate. There were no differences found in plasma ET-1 levels, urinary ET-1-Ll, and sodium excretion rates between the control and hypertensive groups. After saline infusion, ten hypertensive patients showed nonexaggerated natriuresis, and the 24-h urinary ET-1-Ll excretion (47.0 ± 4.0 pmol/day), collected during the day of saline infusion, was significantly lower than that of the control group (86.3 ± 10.0 pmol/day) or the exaggeratedly natriuretic hypertensive patients (91.7 ± 8.4 pmol/day). Our results suggest that renal ET-1 may be responsible for the renal handling of sodium homeostasis, and alteration of renal ET-1 synthesis may be a contributory factor in the pathogenesis of essential hypertension and salt sensitivity.     

Urinary excretion of high molecular weight adiponectin is an independent predictor of decline of renal function in type 2 diabetes

Adiponectin and urinary adiponectin excretions have been ascribed a function in glomerular physiology and seem to indicate vascular disease in diabetes. The aim of this study was to compare the urinary excretion of albumin and adiponectin as predictors for decline of renal function in patients with type 2 diabetes and early kidney disease. Over 141 patients were screened for renal function (estimated GFR, ml/min*1.73 m²), albumin excretion rate (AER, mg/24 h), total as well as high molecular weight (HMW) urinary adiponectin excretion (ng/mol u-creatinine). AER and adiponectin excretion were studied as predictors of renal function after 1 year. After 1 year, 36 patients were in the upper quartile of eGFR decline and defined as progressors (delta eGFR = ? 12.3 ± 6.3) while the remaining 105 patients were defined as non-progressors (delta eGFR = 1.4 ± 6.0). At baseline, HMW-adiponectin excretion was positively correlated with HbA_1c (p < 0.001) and negatively with eGFR (p < 0.001), but not with AER (p = 0.14). Progressors showed increased urinary HMW-adiponectin at baseline (158[IQR41/479] vs. 65[24/168] ng/mol; p < 0.01), while total adiponectin (182[101/1534] vs. 345[118/1361] ng/mol) and AER (48[23/109] vs. 46[25/108] mg/24 h) excretion showed no differences between the groups. Multivariate logistic regression showed that HMW-adiponectin excretion was an independent predictor of renal progression in all patients (OR 1.86 [95 % CI 1.34–2.59]; p < 0.01), especially in those (n = 45) with normal AER at baseline (OR 2.16 [95 % CI 1.1–4.56]; p < 0.05). Urinary HMW-adiponectin but not AER improved the prediction of progressors in ROC analysis (AUC 0.72 [95 % CI 0.63–0.81] vs. 0.80 [95 % CI 0.71–0.90], p < 0.05). In conclusion, urinary HMW-adiponectin excretion may identify diabetes patients at increased risk for progression of kidney disease.     

Improvement of plasma endothelin-1 and nitric oxide in patients with systemic sclerosis by bosentan therapy

The aim of this study was to evaluate the effects of bosentan on plasma endothelin-1 (ET-1) and nitric oxide (NO) as pulmonary hypertension (PH)-associated biochemical markers in patients with systemic sclerosis (SSc). Twenty-four SSc patients receiving bosentan for 24 weeks were registered in this prospective observational study. Ten patients were complicated with clinically suspected PH. Plasma levels of ET-1 and NO were assessed at baseline and after 24 weeks of treatment in SSc patients and in 15 healthy controls. Plasma levels of ET-1 and NO at baseline were significantly higher in SSc patients than in healthy controls (p < 0.000), and they were also significantly higher in SSc patients with PH than in those without PH (p < 0.01). Plasma ET-1 levels were significantly decreased after 24 weeks of bosentan therapy (p < 0.0001), and ET-1 levels of SSc patients with PH decreased to a level comparable to that in patients without PH. In the 10 SSc patients with PH, changes in plasma ET-1 levels during the 24 weeks of the study were significantly larger in the 5 patients whose functional class (FC) improved than in the 5 patients whose FC was unchanged (p < 0.05). Plasma NO levels were also slightly decreased in SSc patients after 24 weeks of bosentan therapy. Plasma ET-1 levels could reflect the presence and severity of PH in SSc patients. Additionally, changes in plasma ET-1 levels may indicate the response to bosentan therapy in SSc patients with PH.     

Effect of insulin on renal sodium and uric acid handling in essential hypertension

In normal subjects, insulin decreases the urinary excretion of sodium, potassium, and uric acid. We tested whether these renal effects of insulin are altered in insulin resistant hypertension. In 37 patients with essential hypertension, we measured the changes in urinary excretion of sodium, potassium, and uric acid in response to physiological euglycemic hyperinsulinemia (by using the insulin clamp technique at an insulin infusion rate of 6 pmol/min/kg). Glucose disposal rate averaged 26.6 ± 1.5 μmol/min/kg, ie, 20% lower than in normotensive controls (33.1 ± 2.1 μmol/min/kg, P = .015). In the basal state, fasting plasma uric acid concentrations were higher in men than women (P < .001), were positively related to body mass index (r = 0.38, P = .02), waist/hip ratio (r = 0.35, P < .05), and serum triglyceride levels (r = 0.59, P = .0001), and negatively related to HDL cholesterol concentrations (r = −0.59, P = .0001) and glucose disposal rate (r = 0.42, P < .01). Uric acid clearance, on the other hand, was inversely related to body mass index (r = 0.41, P = .01), plasma uric acid (r = 0.65, P < .0001) and triglyceride concentrations (r = 0.39, P < .02), and directly related to HDL cholesterol levels (r = 0.52, P < .001). During insulin infusion, blood pressure, plasma uric acid and sodium concentration, and creatinine clearance did not change. In contrast, hyperinsulinemia caused a significant decrease in the urinary excretion of uric acid (2.67 ± 0.12 to 1.86 ± .14 μmol/min/1.73 m², P = .0001), sodium (184 ± 12 to 137 ± 14 μmol/min/1.73 m², P = .0001), and potassium (81 ± 7 to 48 ± 4 μmol/min/1.73 m², P = .0001). Both in absolute terms (clearance and fractional excretion rates) and percentagewise, these changes were similar to those found in normotensive subjects. Insulin-induced changes in urate excretion were coupled (r = 0.55, P < .0001) to the respective changes in sodium excretion. In hypertensive patients, higher uric acid levels and lower renal urate clearance rates cluster with insulin resistance and dyslipidemia. Despite insulin resistance of glucose metabolism, acute physiological hyperinsulinemia causes normal antinatriuresis, antikaliuresis, and antiuricosuria in these patients.     

Normal-range albuminuria in healthy subjects increases over time in association with hypertension and metabolic outcomes

Albuminuria is a prognostic factor for mortality and cardiovascular events, even at low levels. Changes in albumin excretion are associated with end-stage renal disease and hypertension (HTN) in cohorts including high-risk participants. We aimed to investigate the evolvement of albumin excretion in healthy individuals with normal kidney function and normoalbuminuria, and possible associations with HTN and metabolic outcomes. The study cohort consisted of 1967 healthy adults with normal kidney function (estimated glomerular filtration rate ≥ 90 mL/min/1.73 m²; urine albumin to creatinine ratio [ACR] < 30 mg/g). Delta ACR slope was calculated as ACR difference between two consecutive visits divided by the time interval. During a mean follow-up period of 93.8 months, mean delta ACR slope was 0.27 ± 3.29 mg/g/year and was higher in participants with age >40 years, obesity, a high waist circumference, higher baseline ACR, HTN, prediabetes, and metabolic syndrome. Delta ACR slopes in the upper quartile predicted diabetes (OR = 1.31, P = .027) and albuminuria (4.34, P < .001). Upper quartile of ACR slopes correlated with a higher risk for new-onset HTN (1.249, P = .031). Delta systolic and diastolic blood pressures were associated with ACR slopes in addition to age, body mass index, and baseline ACR. In conclusion, accelerated change in ACR correlates with HTN and diabetes in healthy individuals with normal kidney function and normoalbuminuria.     

Pressure-dependent,enhanced natriuretic response to low-dose,atrial natriuretic peptide infusion in essential hypertension

Abstract. Objective. To examine whether the effect of atrial natriuretic peptide (ANP) on renal glomerular and tubular segmental handling of sodium in patients with essential hypertension is pressure dependent. Design. Part 1. The renal effects of a low-dose continuous infusion (10 ng kg^?1 min^?1) with ANP for 1 h were compared in 10 untreated essential hypertensives (EH) and 13 normotensive control subjects (CS). Part 2. The hypertensives were studied on another day with ANP infusion during preceding acute BP reduction with sodium nitroprusside infusion (NP). The results were compared with those obtained during infusion with ANP + placebo (Part 1). Methods. Lithium clearance was used to estimate the proximal tubular reabsorption of sodium. Results. Part 1. Atrial natriuretic peptide caused an exaggerated increase in urinary sodium excretion (+ 102 vs. + 38%; P < 0.05), fractional excretion of sodium (+ 80 vs. + 37%; P < 0.05), and urinary output (+ 56 vs. + 8.3%; P < 0.05) in EH compared with CS. Glomerular filtration rate and filtration fraction increased to the same degree in both groups. Absolute lithium clearance (C_L1) increased and FE_L1 tended to increase (P = 0.061) in EH, but these were unchanged in CS. The increase in plasma cyclic guanosine 5′-phosphate (cGMP) and urinary excretion of cGMP and the decrease in plasma aldosterone during ANP infusion were the same in the two groups. Part 2. During NP infusion the natriuresis caused by ANP in EH was reduced (+ 51 vs. +99%; P <0.05). The relative changes in GFR, C_L1, and FE_L1 during ANP infusion were not affected by the preceding BP reduction with NP. Mean arterial pressure was reduced from 122 to 101 mmHg during NP infusion. The relative increase in sodium excretion in EH was significantly correlated to mean arterial pressure. Conclusions. Low-dose ANP infusion causes an exaggerated natriuresis in untreated essential hypertensives due to a more pronounced reduction in tubular reabsorption. After BP reduction, the natriuresis induced by ANP in essential hypertensives is decreased, probably due to a less pronounced reduction in tubular reabsorption beyond the proximal tubules. We suggest that the enhanced natriuretic response to ANP in EH is secondary in some degree to the elevated systemic pressure.     

Sex differences in renal medullary endothelin receptor function in angiotensin II hypertensive rats

We hypothesized that angiotensin (Ang) II hypertensive rats have impaired natriuresis after renal medullary endothelin (ET) B receptor stimulation that would be more evident in male versus female rats. Acute intramedullary infusion of the ET(B) agonist sarafotoxin 6c in normotensive male rats increased sodium excretion from 0.51±0.11 μmol/min during baseline to 1.64±0.19 μmol/min (P<0.05) after S6c. After 2 weeks of Ang II infusion (260 ng/kg per minute SC), male rats had an attenuated natriuretic response to S6c of 0.62±0.16 μmol/min during baseline versus 0.95±0.07 μmol/min after S6c. In contrast, ET(B)-dependent natriuresis was similar in female hypertensive rats (0.48±0.07 versus 1.5±0.18 μmol/min; P<0.05) compared with normotensive controls (1.05±0.07 versus 2.14±0.24 μmol/min; P<0.05). Because ET(A) receptors also mediate natriuresis in normotensive female rats, we examined ET(A) receptor function in female Ang II hypertensive rats. Intramedullary infusion of ET-1 increased sodium excretion in both hypertensive and normotensive female rats, which was partially blocked by the ET(A) antagonist BQ-123. Maximum ET(B) receptor binding in inner medullary membrane preparations was comparable between vehicle and Ang II hypertensive females; however, maximum ET(B) binding was significantly lower in male hypertensive rats (1952±251 versus 985±176 fmol/mg; P<0.05). These results indicate that renal ET(B) function is impaired in male Ang II hypertension attributed, at least in part, to a reduced number of ET(B) binding sites. Furthermore, renal ET receptor function is preserved in female rats during chronic Ang II infusion, suggesting that renal ET receptor function could serve to limit hypertension in females compared with males.     

Effect of Loop Diuretics on the Fractional Excretion of Urea in Decompensated Heart Failure

BackgroundFractional excretion of urea (FEUrea) is often used to understand the etiology of acute kidney injury (AKI) in patients receiving diuretics. Although FEUrea demonstrates diagnostic superiority over fractional excretion of sodium (FENa), clinicians often assume FEUrea is not affected by diuretics.ObjectiveTo assess the intravenous loop diuretic effect on FEUrea.MethodsWe analyzed a prospective cohort (n=297) hospitalized with hypervolemic heart failure at Yale New Haven Hospital System. FENa and FEUrea were calculated at baseline and serially after diuretics. The change in FEUrea at peak diuresis was compared with the pre-diuretic baseline.ResultsMean baseline FEUrea was 35.2% ± 10.5% and increased by a mean 5.6% ± 10.5% following 80 mg (40–160 mg) of furosemide equivalents (P < .001). The magnitude of change in FEUrea was clinically important as the distribution of change in FEUrea was similar to the overall distribution of baseline FEUrea. Change in FEUrea was related to the diuretic response (r = 0.61, P < .001), with a larger FEUrea increase in diuretic responders (8.8%, interquartile range [IQR]: 1.8–16.9) than non-responders (1.2%, IQR: −3.2 to 5.5; P < .001). Diuretic administration reclassified 27% of patients between low and high FEUrea groups across a 35% threshold. Neither change in FEUrea nor percentage reclassified out of a low FEUrea category differed between patients with and without AKI (P > .63 for both).ConclusionsFEUrea is meaningfully affected by loop diuretics. The degree of change in FEUrea is highly variable between patients and commonly of a magnitude that could reclassify across categories of FEUrea.     

The effect of renal hyperfiltration on urinary inflammatory cytokines/chemokines in patients with uncomplicated type 1 diabetes mellitus

Aims/hypothesis

High intraglomerular pressure causes renal inflammation in experimental models of diabetes. Our objective was to determine whether renal hyperfiltration, a surrogate for intraglomerular hypertension, is associated with increased excretion of urinary cytokines/chemokines in patients with type 1 diabetes mellitus.

Methods

Blood pressure, renal haemodynamic function (inulin and para-aminohippurate clearances for glomerular filtration rate (GFR) and effective renal plasma flow (ERPF), respectively) and urine samples were obtained during clamped euglycaemia in individuals with type 1 diabetes with either hyperfiltration (GFR determined using inulin [GFR_INULIN] ≥135 ml? min^?1 1.73 m^?2, n?=?28) or normofiltration (n?=?21) and healthy control individuals (n?=?18).

Results

Baseline clinical characteristics, dietary sodium and protein intake and blood pressure levels were similar in the diabetic and healthy control groups. In addition, HbA_1c levels were similar in the two diabetic groups. As expected baseline GFR was higher in hyperfilterers than either normofiltering diabetic patients or healthy control patients (165?±?9 vs 113?±?2 and 116?±?4 ml min^?1 1.73 m^?2, respectively, p?<?0.01). ERPF and renal blood flow were also comparatively higher and renal vascular resistance was lower in hyperfiltering patients (p?<?0.01). Hyperfiltering diabetic patients had higher excretion rates for eotaxin, IFNα2, macrophage-derived chemokine, platelet-derived growth factor (PDGF)-AA, PDGF-AB/BB and granulocyte-macrophage colony-stimulating factor (p?≤?0.01). Urinary monocyte chemoattractant protein (MCP)-1 and RANTES (regulated on activation, normal T expressed and secreted) excretion was also higher in hyperfiltering vs normofiltering diabetic individuals (p?<?0.01) and fibroblast growth factor-2, MCP-3 and CD40K excretion was elevated in hyperfiltering diabetic individuals vs healthy controls (p?<?0.01).

Conclusions/interpretation

Renal hyperfiltration is associated with increased urinary excretion of inflammatory cytokines/chemokines in patients with uncomplicated type 1 diabetes.     

Effect of sleeve gastrectomy on hypertension

The objective of this study was to determine the effect of laparoscopic sleeve gastrectomy (LSG) on blood pressure in private practice settings. This study involved a retrospective review of 870 consecutive adult patients >18 y of age who underwent LSG over a period of 12 mo in a private bariatric surgery center. Data were collected from the preoperative and postoperative follow-up visits at 1, 3, 6, and 12 mo. The study population consists of 694 hypertensive and 176 normotensive patients. From the baseline to 12 mo after LSG, (1) mean body weight/body mass index decreased from 123 kg/44 kg/m² to 94 kg/34 kg/m² (P < .001); (2) mean systolic/diastolic blood pressure in hypertensive patients decreased from 131.9/79.9 to 127.6/77.1 mm Hg (P < .001); 3) only mean systolic blood pressure decreased in normotensive patients from 117.5 to 114.0 mm Hg (P < .001). One month after LSG, mean systolic blood pressure had decreased from 131.9 to 126.2 mm Hg (P < 0. 001) and the average number of antihypertensive medications per patient declined from 1.5 at the baseline to 0.6 (P < .001). Over the following 11 mo, blood pressure remained stable despite reduced antihypertensive therapy. Patients requiring more than two antihypertensive agents fell from 49% at the baseline to 22% at 12 mo. Hypertension resolved in 34% of patients. Linear regression analysis showed no association between change in body weight and change in systolic blood pressure. Within 1 mo of LSG, hypertensive patients experienced a significant decline in systolic blood pressure and antihypertensive therapy that remains unchanged at 12 mo in the face of major reductions in antihypertensive medications. Weight loss and blood pressure reduction may not be directly related.     

Rapid hypotensive response to fasting in spontaneously hypertensive rats

This study examined changes in renal function and mean arterial pressure (MAP) in spontaneously hypertensive (SHR) and Wistar-Kyoto (WKY) rats during 48 h of fasting, independent of changes in sodium intake. Spontaneously hypertensive rats (n = 17) and WKY rats (n = 10) were instrumented with artery and vein catheters and sodium intake was clamped at 2.1 mEq/day. By day 2 of fasting, MAP decreased −10 ± 1 mm Hg (P < .001) in SHR, but did not change significantly in WKY rats. Heart rate decreased significantly in both groups by day 2 of fasting and there was a significant increase in urine volume and sodium excretion. Thus, fasting caused a rapid decrease in MAP in SHR that was not due to decreased sodium intake, but may be related, in part, to volume loss and improved renal excretory function.     

NOCTURNAL NATRIURESIS IN HYPERTHYROIDISM

We measured urine flow and the renal excretion of total solute, sodium, potassium and calcium in eleven patients with hyperthyroidism before and after treatment. Mean nocturnal sodium excretion was significantly greater (P < 0·05) during hyperthyroidism and was unaccompanied by any significant alterations in day time or 24-h values. As a result of this nocturnal natriuresis in hyperthyroidism significant changes were noted in the ratios of day/night sodium excretion (P < 0·005) and urinary flow (P < 0·05). The change in ratio of day/night sodium excretion resulting from treatment of hyperthyroidism was shown to correlate significantly with the change in plasma total triiodothyronine (r=0·73, P < 0·01). Twenty-four hour urinary calcium output was significantly greater (P < 0·02) in hyperthyroidism but there was no significant alteration in the day/night pattern of excretion.     

Correlated plasma elastase and sera cytotoxicity in eclampsia A possible role of endothelin-1 induced neutrophil activation in preeclampsia-eclampsia

The activation of neutrophils was studied in preeclampsia (n = 10) and eclampsia (n = 20) compared to normotensive controls (n = 10) and non-pregnant essential hypertensives (n = 10). Plasma elastase levels were raised in preeclampsia (0.53 ± 0.32 μg/mL, P < .002) and eclampsia (1.26 ± 0.8 μg/mL, P < .001) respectively compared to normal pregnancies (0.032 ± 0.009 μg/mL). The plasma elastases were more elevated in eclamptic cases compared to essential hypertensive (0.53 ± 0.27 μg/mL; P = .01) patients. We analyzed the correlation among elastase values, systolic (SBP), mean blood pressures (MBP), endothelin-1 (ET-1) levels and sera cytotoxicity (as measured by fura-2 release from human umbilical venous endothelial cell culture) in eclamptic cases. SBP and MBP were significantly correlated with plasma elastase levels in preeclampsia (r = 0.67, 0.63, respectively; P < .03) and eclampsia (r = 0.49, 0.49, respectively; P < .02). ET-1 levels were correlated with SBP (P = .003) and MBP (P = .001) and corresponding elastase levels (r = 0.606, P < .003) in eclamptic patients. Doses of 10, 25, and 50 pmol/mL of ET-1 increased elastase release in human neutrophil cultures dose and time dependently. Cytotoxicity of eclamptic sera correlated (P < .001) to the corresponding plasma elastase values. Therefore, this study suggests that neutrophil activation and ET-1 induced neutrophil activation occurs in this disease     

EFFECT OF NICARDIPINE VERSUS ENALAPRIL ON PLASMA ENDOTHELIN-1 IN HYPERTENSIVE PATIENTS WITH TYPE 2 DIABETES MELLITUS

We compared the effects of dihydropyridine type Ca channel blocker slow-release nicardipine and angiotensin converting enzyme inhibitor enalapril on plasma endothelin-1 (ET-1) levels in hypertensive type 2 diabetic patients (n = 20). Nicardipine or enalapril was administered for 6 months by a crossover design. Nicardipine and enalapril comparably lowered blood pressure. Enalapril significantly reduced urinary albumin excretion in microalbuminuric patients, whereas nicardipine did not. Urinary β2-microglobulin excretion was significantly increased during nicardipine treatment. However, both drugs significantly reduced plasma ET-1 as compared with pretreatment levels, close to that in healthy control (2.9 ± 0.3 pg/ml in control, 4.8 ± 0.3 pg/ml before treatment, 3.2 ± 0.3 pg/ml during nicardipine vs before treatment p<0.05, 2.9 ± 0.4 pg/ml during enalapril vs before treatment p<0.01). The decrease in plasma ET-1 was significantly correlated with the increase in natriuresis in normoalbuminuric patients treated with enalapril (r=?0.82, p<0.01) but not in those treated with nicardipine. Although nicardipine and enalapril had different renal effects, both drugs equally suppressed plasma ET-1 levels in hypertensive patients with type 2 diabetes.     

Blood Pressure and Metabolic Responses to Moderate Sodium Restriction in Isradipine-Treated Hypertensive Patients

This multicenter, randomized, controlled clinical trial assessed the influence of sodium chloride intake on the antihypertensive effect of the calcium channel blocker isradipine. Participants with uncomplicated hypertension controlled by isradipine entered a 4-week sodium-restricted (60 to 80 mmol/24 h) period. Participants with urinary sodium levels <120 mmol/24 h (n = 99) were randomized to placebo or sodium chloride (100 mmol/24 h) for 4 weeks, and then crossed over to the alternative treatment for an additional 4 weeks. Mean baseline systolic blood pressure was 151.9 ± 16.7 mm Hg (mean ± SD). During open-label isradipine treatment, systolic blood pressures for ad libitum sodium chloride and restriction were 134.1 ± 11.1 and 132.1 ± 12.2 mm Hg respectively; for double-blind sodium chloride restriction and supplementation: 133.6 ± 12.6 and 138.5 ± 12.8 mm Hg (P < .01). Urinary sodium excretion values for open-label isradipine ad libitum versus restricted were 140.6 ± 61.9 versus 76.9 ± 32.4 mmol/24 h; for double-blind restricted versus supplemented, sodium excretion was 120.5 ± 68.9 v 175.9 ± 68.7 mmol/24 h (P ≤ .0001). Changes in urinary sodium excretion were not predictive of variations in blood pressure. Urinary sodium excretion during sodium restriction correlated directly with HDL-cholesterol (P < .02) and inversely with total cholesterol:HDL-cholesterol (P = .02), despite decreased total and saturated fat intake (P < .01). Sodium restriction was associated with significant reductions (P < .01) in virtually all macronutrients and electrolytes, and thus had an adverse impact on overall nutrition. The antihypertensive action of isradipine was not enhanced by dietary sodium chloride restriction, and the lipoprotein profile was least favorable with sodium chloride restriction.     

Factores asociados a la compensación de la función renal tras la nefrectomía para donación

Introduction

Kidney transplant donors lose 50% of their renal mass after nephrectomy. The remaining kidney compensates for this loss and it is estimated that 70% of the baseline renal function prior to donation is recovered. Factors associated with post-donation renal compensation are not well understood.