Effect of weight loss through laparoscopic gastric banding on blood pressure, plasma renin activity and aldosterone levels in morbid obesity

Background and aimsSeveral mechanisms are probably involved in obesity-related hypertension. This study was aimed to investigate the effect of significant weight loss on blood pressure and plasma renin activity (PRA) and aldosterone levels, other then on metabolic profile, in normotensive and hypertensive obese subjects.Methods and resultsForty hypertensive and 55 normotensive obese subjects were studied under basal conditions and again 1 year after significant weight loss obtained through laparoscopic adjustable gastric banding (LAGB). Weight, waist circumference, blood glucose, insulin, electrolytes (Na and K), lipids and supine and upright PRA and aldosterone were evaluated. All parameters evaluated improved, except for total cholesterol, and electrolytes that did not change. Blood pressure decreased in hypertensive subjects, with a concordant decrease in PRA and supine aldosterone levels, not observed in normotensive patients.ConclusionWeight loss is associated with reduction of blood pressure and of PRA and aldosterone levels in obese hypertensive subjects.     

Reactivity to norepinephrine and effect of sodium on blood pressure during weight loss

Eighteen moderately obese middle-aged men with untreated mild hypertension were randomized to two groups and placed on a low energy diet regimen for 9 to 11 weeks. In Group I (n = 10) the amount of sodium chloride in the diet maintained the urinary sodium excretion at the predieting level. Mean body mass was reduced by 9.1 +/- 0.7 (SEM) kg. Mean intra-arterial pressure showed no significant change. There were significant decreases in heart rate (p less than 0.05) and urinary norepinephrine excretion (p less than 0.05) but not in plasma concentration of norepinephrine. In Group II (n = 8) energy as well as sodium intake was restricted, with a 95 +/- 22 mmol/24 hour reduction of urinary sodium excretion. Body mass decreased by 9.3 +/- 1.1 kg, and mean arterial pressure decreased by -18.9 to -4.3 mm Hg (95% confidence interval). There were also significant reductions in heart rate (p less than 0.001) and plasma norepinephrine concentrations (p less than 0.01) but not in urinary norepinephrine excretion. The pressor response (mean arterial pressure) to norepinephrine infusion at different dose rates was significantly elevated (p less than 0.05) in Group I during dieting in comparison with baseline. The blood pressure response to norepinephrine during dieting in patients in Group II was not changed from baseline.(ABSTRACT TRUNCATED AT 250 WORDS)     

Humoral effect of norepinephrine on renin release in humans

We compared the effects of infused norepinephrine (NE) to another alpha-adrenergic agonist, phenylephrine, in order to understand better the influence of circulating NE on plasma renin activity (PRA) in man. In matched groups of normotensive men, NE (80 ng/min/kg) or phenylephrine (800 ng/min/kg) raised blood pressure by 15 to 20 mm Hg and caused reflex decreases in heart rate of 8 to 10 beats per minute. Infused phenylephrine suppressed PRA by about 15%, whereas NE increased PRA by about 40% (P less than .02). This differential effect of alpha-agonists on PRA defines an important humoral effect of NE, which should be considered to be a "cardiovascular hormone."     

Effects of calcium on renin and aldosterone

A series of experiments was undertaken to assess the effects of calcium administration, in vivo, on renin and aldosterone secretion. In the anesthetized dog, renin secretion was decreased by renal arterial infusions of calcium chloride and calcium gluconate; aldosterone excretion was not affected. In the sodium chloride-deprived rat, dietary calcium chloride loading decreased plasma renin activity, whereas calcium gluconate did not. Both calcium salts increased aldosterone production. In the non-filtering, denervated, papaverine-treated dog kidney, renin release was stimulated by renal arterial infusion of verapamil. In the rat, chronic oral verapamil administration decreased plasma aldosterone but had no effect on renin. In humans, chronic oral verapamil decreased aldosterone responsiveness to infusion of angiotensin II. Thus, in vivo renin release is inhibited by hypercalcemia and stimulated by blocking calcium transport; conversely, aldosterone production is stimulated by a high calcium intake and inhibited by blocking calcium transport. These effects of calcium on renin and aldosterone may have implications for understanding the putative relation between calcium and hypertension.     

High-dose spironolactone changes renin and aldosterone levels in acutely decompensated heart failure

BackgroundIn acutely decompensated heart failure (ADHF) patient's higher aldosterone levels correlate with worse postdischarge outcomes, suggesting that further modulation of the mineralocorticoid system during or immediately after hospitalization might favorably improve outcomes.Methods and resultsThis was an observational, retrospective secondary analysis of a study including 100 patients with ADHF. In that study 50 patients were submitted to spironolactone treatment (50–100 mg/day). A higher proportion of patients with renin levels above 16.5 pg/mL and aldosterone levels above 100 ng/dL were observed in subjects submitted to spironolactone treatment (44.7% vs. 66.7% and 56% vs. 64.7%, respectively, both p < 0.05). In the group of patients submitted to spironolactone treatment the proportion of patients with renin and aldosterone levels above the cutoff had a significant increase from baseline to day 3 (24–32% and 16–44%, respectively, both p < 0.05). Log renin and aldosterone were higher in patients with renin and aldosterone levels above the cutoff point (both p < 0.05).ConclusionsHigh-dose spironolactone added to standard ADHF therapy induces an additional increase in renin and aldosterone levels. Whether higher levels of renin and aldosterone due to the reactive response to full MRA still have prognostic value requires further investigation.     

The responses of norepinephrine, renin and aldosterone to standing in diabetic patients with orthostatic hypotension

Autonomic neuropathy is one of the complications of diabetes, and several lines of evidence, supporting that sympathetic neural dysfunction may play the major role in the orthostatic hypotension (OH) of diabetic patients have been presented. In this paper the responses of plasma norepinephrine (PNE), plasma renin activity (PRA) and plasma aldosterone (PAC) to upright standing were studied in 17 diabetic patients without OH, 25 diabetics with OH and 17 age-matched, non-diabetic normotensives (controls). All were kept on a 200mEq sodium diet. Assay procedure for PNE was high-performance liquid chromatography with trihydroxyindol method and fluorimetric detection using dihydroxybenzylamine as internal standard. Intra- and inter-assay coefficient variations by this method were 3.4 and 5.8% respectively. PRA and PAC were determined by radioimmunoassay. Total blood volume was examined by the plasma tracer method using 131I-HSA and expressed in percent normal. Mean PNE level in the non-diabetic controls was 217 pg/ml in recumbency and increased to a level of 551 at 15 minutes on standing. The PNE responses to standing in the diabetic subjects without OH (defined as group I) were not significantly different from those in the controls. In the diabetics with OH, 14 cases, with the PNE increments less than 1SD below the mean in the controls, were defined as group III, and discriminated from other 11 subjects with OH (group II). PNE levels in group III were significantly lower than in the controls at both recumbency and upright posture. PRA was significantly elevated by standing in the controls and the diabetics except for group II. PRA in all the diabetic groups was significantly lower than in the controls, at both recumbent and upright. The mean values of PAC in the diabetics but group II at supine were significantly lower than those of the control group. PAC levels increased after standing contemporaneously with PRA, though significant rise in group II was shown without PRA response. Total blood volume was significantly (p less than 0.025) decreased in only group II. The results suggest: 1) PNE was normal in the diabetic patients without OH, 2) there are at least two types of OH in diabetes mellitus: one is hypoadrenergic and the other hypovolemic, 3) adrenergic neuropathy may be a cause of low PRA in diabetics with OH but another factor may also be involved in both with and without OH, 4) low PRA is a main factor of low PAC in diabetics (group I and III), but the dissociation between PRA and PAC responses to orthostasis is present in some cases (group II), which reflects disturbances in other regulatory mechanisms of aldosterone secretion.     

Diet,weight loss,and cardiovascular disease prevention

Opinion statement Body weight, like cholesterol and blood pressure, are continuous variables. Overweight results when energy intake as food exceeds energy expenditure from exercise for a considerable period of time. When body weight becomes sufficiently high, it poses a risk to cardiovascular and metabolic health. The types of treatments considered by the physician and discussed with a patient should be based on this risk-benefit assessment. The body mass is the basic measurement for this assessment, and should be part of the “vital signs” when a patient is first evaluated by the medical staff. When the body mass index (BMI) is below 25 kg/m², there is little risk from the body weight, but because obesity is a “stigmatized” condition, many patients, particularly women, desire to lose weight even within the normal range. For this purpose, a high-quality diet like the Dietary Approaches to Stopping Hypertension (DASH) diet at a reduced-calorie intake would be our recommendation. When the BMI is above 25 kg/m², patients deserve dietary advice, but in addition to a reduced-calorie DASH-like diet, this is a place to consider using “portion-control” strategies, such as the nutrition labels that manufacturers provide on canned and frozen foods to guide patients in reducing calorie intake. In overweight individuals at high risk (ie, those with a BMI above 30 kg/m² or impaired glucose tolerance, hypertension, or the metabolic syndrome), the use of orlistat or sibutramine along with diet, exercise, lifestyle changes, and portion control should be considered. When the BMI is above 35 kg/m², bariatric surgery should also be discussed as an option for the "at-risk" individual. Evidence reviewed here shows that modest weight losses of 5% to 10% can reduce the risk of conversion from impaired glucose tolerance to diabetes and can maintain lower blood pressure over extended periods. All of the approaches described above can produce weight losses of this magnitude.     

The effect of chlorpromazine on plasma renin activity and aldosterone in man.

The response of plasma renin activity (PRA) and aldosterone to the intravenous administration of chlorpromazine was determined in schizophrenic patients while they were supine and on a normal sodium diet. In all subjects PRA and aldosterone increased during chlorpromazine administration with little or no change in blood pressure. The maximum PRA and aldosterone levels occurred 60 min after the higher dose of chlorpromazine. These data suggest that chlorpromazine affects the renin-angiotensin-aldosterone system and it may interfere with the evaluation of this system in patients receiving this drug.     

Plasma levels and hepatic extraction of renin and aldosterone in alcoholic liver disease.

Arterial plasma levels and hepatic extraction of renin and aldosterone (ALDO) were measured in 24 patients with alcoholic liver disease and in 14 normal subjects being evaluated as prospective kidney donors. Patients with liver disease had higher plasma concentrations and lower fractional hepatic extractions of both renin and ALDO than the normal subjects. The quantity of renin extracted by the liver was highly correlated with plasma renin in both normal subjects and patients. Plasma ALDO concentration was positively correlated with plasma renin (p less than 0.001) but not with serum sodium, potassium or albumin concentration, inferior vena cava pressure, corrected hepatic venous wedge pressure, plasma volume or sulfobromophthalein storage or transport. Sixteen patients were restudied after one month. Six had received 40 mg/day of prednisolone, and the remaining 10 had received a placebo. Neither group had a change in plasma volume, corrected hepatic venous wedge pressure, plasma concentration or hepatic extraction of renin or ALDO. Serum albumin concentration increased and inferior vena cava pressure decreased with prednisolone therapy. These studies document high plasma levels and impaired hepatic extraction of renin and ALDO in patients with liver disease that are not corrected by short-term prednisolone therapy.     

Decreases in renin and aldosterone secretion in alloxan diabetes: an effect of insulin deficiency

The effect in the rat of alloxan diabetes (with and without insulin treatment) on renin and aldosterone secretion was examined. Rats with diabetes for 7 weeks were found to have lower PRA than nondiabetic controls. The decrease in PRA appeared to result from insulin deficiency since PRA was normal in diabetic rats given insulin. In a second set of animals, which were killed after 3 weeks, in vitro measurements of aldosterone production by perifused adrenal capsular tissue were carried out. Production of aldosterone was greatest by adrenal capsular tissue from insulin-treated diabetic rats where both basal and potassium-stimulated aldosterone production were higher than diabetic rats not given insulin. Although the reduced aldosterone production associated with untreated diabetes may have been a result of reduced in vivo exposure of adrenal tissue to angiotensin II, a chronic adrenotrophic influence of insulin could not be ruled out. In summary, insulin appears to be necessary for normal renin and aldosterone secretion in the diabetic rat.     

Effect of weight loss after weight loss surgery on plasma N-terminal pro-B-type natriuretic peptide levels

Natriuretic peptides have multiple beneficial cardiovascular effects. Previous cross-sectional studies have indicated that obese subjects have lower natriuretic peptide concentrations than those of normal weight. It is not known whether this relative natriuretic peptide deficiency is reversible with weight loss. We studied 132 obese subjects undergoing weight loss surgery with serial measurement of plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP) concentrations at preoperative, early (1 to 2 months), and late postoperative (6 months) points. In addition, 20 subjects also underwent echocardiography at baseline and 6 months after surgery. Significant weight loss was observed after surgery (median body mass index 45.1, 41.0, and 32.9 kg/m(2) for the 3 corresponding points, analysis of variance p <0.001). The median NT-proBNP levels increased substantially (31.6, 66.9, and 84.9 pg/ml; p <0.001). The average intrasubject increase in NT-proBNP at the 2 postoperative points was 3.4 and 5.0 times the preoperative level (p <0.001 for both points vs preoperatively). In the multivariate regression models adjusted for clinical characteristics and insulin resistance, the strongest predictor of the change in NT-proBNP level 6 months after weight loss surgery was the change in weight (p = 0.03). Echocardiography showed a mean intrasubject reduction in left ventricular mass index of 18% (p <0.001) and mild improvements in diastolic function, with no change in ejection fraction. In conclusion, we have demonstrated that weight loss is associated with early and sustained increases in NT-proBNP concentrations, despite evidence of preserved systolic and improved diastolic function. These findings suggest a direct, reversible relation between obesity and reduced natriuretic peptide levels.     

Plasma renin and aldosterone measurements in low renin hypertensive states.

Plasma renin concentrations are extremely low, requiring high sensitivity methods to detect low renin hypertensive states. Moreover, plasma prorenin must not cryoactivate to renin to avoid falsely high values. The enzyme kinetic plasma renin activity (PRA) test has the required sensitivity, whereas direct renin assays and PRA tests with short incubation times are usually not accurate enough. Test specificity is essential for plasma aldosterone. The Nichols Advantage aldosterone assay is fast and automated but requires great attention to quality control. Here, the impact of renin on the aldosterone:renin ratio as a screening test for primary aldosteronism is reviewed. A sensitive plasma renin test is essential for the diagnosis of low renin hypertensive states and, currently, can be consistently achieved only with the PRA radioimmunoassay.     

The effect of orlistat-induced weight loss on interleukin-6 and C-reactive protein levels in obese subjects

OBJECTIVE: Inflammation plays a major role in the pathogenesis of atherosclerosis. Obesity is an independent risk factor for cardiovascular disease, which may be mediated by increased secretion of proinflammatory cytokines by adipose tissue. The aim of this study is to investigate changes in the inflammatory markers interleukin-6 (IL-6) and high-sensitivity C-reactive protein (hs-CRP) during weight reduction with orlistat treatment in obese patients. METHODS AND RESULTS: Thirty-six obese (BMI: 36.1 +/- 3.4 kg/m2) and II non-obese (BMI: 22.9 +/- 1.7 kg/m2) subjects were studied. IL-6 and hs-CRP levels were evaluated at baseline. In obese subjects after treatment of orlistat 120 mg three times daily for 6 months, IL-6 and hs-CRP levels were repeated. Levels of circulating IL-6 (p < 0.05) and hs-CRP (p < 0.01) were significantly higher in the obese group than in the non-obese group. Plasma IL-6 (r = 0.29 and p < 0.05) and CRP (r = 0.35 and p < 0.05) concentrations correlated positively with the level of obesity assessed by BMI at baseline. After 6 months of orlistat treatment in obese subjects, the mean weight of the patients decreased by 6.8 kg, the BMI by 3.2 kg/m2. Compared with baseline, weight loss was associated with significant reductions of IL-6 (p < 0.001) and hs-CRP (p < 0.001) levels. CONCLUSION: In summary plasma IL-6 and hs-CRP levels were increased in obese patients. Orlistat-induced weight reduction was associated with decreasing levels of both IL-6 and hs-CRP in obese subjects. Because inflammatory mediators may be directly involved in atherogenesis, this would suggest that interventions to reduce IL-6 and CRP levels could be cardioprotective.     

Plasma phentermine levels, weight loss and side-effects

Fifty women with refractory obesity received phentermine resinate. Seven were withdrawn because of side-effects: three developed severe headaches, one each hypertension, depressive symptoms, breathlessness and palpitations with irritability. The mean weight loss in the 34 who completed the 20-week study was 6.4 kg. Nine lost 10 kg or more. Sustained appetite suppression was related to weight loss. Plasma phentermine concentrations did not correlate with the severity of the obesity problem, the degree of subjective anorexia or with weight loss. Poor initial response to standard dosage of phentermine is unlikely to improve with higher dosage. The individual's response to phentermine is unpredictable and appears to relate to factors other than the plasma drug concentration.     

Relationship of plasma renin activity and aldosterone levels with hemodynamic functions in essential hypertension.

Correlates of plasma renin activity and plasma aldosterone levels with hemodynamic functions were studied in 47 male patients with untreated, permanent essential hypertension. All subjects had a normal creatinine clearance and received a diet of 110 mEq/day of sodium. Supine plasma renin activity was directly correlated with cardiac index (P less than.01) and cardiopulmonary blood volume (P=.01).Percentage changes in plasma renin activity and total peripheral resistance in response to upright position were positively correlated (P less than.001). Supine plasma aldosterone level was directly correlated with stroke index (P less than .001) and negatively correlated with hear rate (P less than .05). No significant correlation of aldosterone level was observed with the other measurements, including plasma renin activity. The study points to the neural sympathetic control of plasma renin activity in essential hypertension and suggests the existence of some interrelationships between aldosterone level and cardiac performance.