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Insulin receptors and renal sodium handling in hypertensive fructose-fed rats
No full textBackground. Insulin resistance and hypertension are present
in Sprague-Dawley rats fed a fructose-enriched diet. In these
rats, insulin might elevate blood pressure via an antinatriuretic
action.
Methods. To investigate the sodium-insulin interaction in
fructose-fed rats, we compared insulin sensitivity, insulin receptor
binding, and insulin receptor mRNA levels in the kidney
and skeletal muscle of rats that were fed standard rat chow or a
fructose-enriched diet (66%) with either low (0.07%), normal
(0.3%), or high (7.5%) NaCl concentrations for 3 weeks.
Results. Systolic blood pressure increased in the fructose-fed
rats receiving the normal and high-salt diet, but not the low-salt
diet.When the rats were fed the low-salt diet, the rate of glucose
infusion required to maintain euglycemia during a hyperinsulinemic
clamp and insulin receptor number and mRNA levels
in skeletal muscle were lower in fructose-fed than control rats.
High-salt diet decreased significantly the rate of glucose disposal
during the clamp and muscular insulin receptor number
and mRNA levels in control, but not fructose-fed rats. During
the low-salt diet, renal insulin receptor number and mRNA
levels were comparable in fructose-fed and control rats and hyperinsulinemia
had comparable acute antinatriuretic effects in
the two groups; when the rats were maintained on the high-salt
diet, the expected decrease in renal insulin receptor number
and mRNA levels occurred in control but not fructose-fed rats
and, consistent with this finding, the antinatriuretic response to
hyperinsulinemia was blunted only in controls. An inverse relationship
between dietary NaCl content and renal insulin receptor
mRNA levels was observed in control but not fructose-fed
rats.
Conclusion. Fructose-fed rats appear to have lost the feedback
mechanism that limits insulin-induced sodium retention
through a down-regulation of the renal insulin receptor when
the dietary NaCl content is increased. This abnormality might
possibly contribute to the elevation of blood pressure in these
rats
Impact of omega-3 polyunsaturated fatty acids on vascular function and blood pressure: relevance for cardiovascular outcomes
No full textAims: To overview the effects of omega-3 polyunsaturated fatty acids (PUFA) on blood vessels and blood pressure and their relevance for cardiovascular prevention.
Data synthesis: The importance of omega-3 PUFA for the cardiovascular system has come under the spotlight during the last decades. These fatty acids are present in variable amounts in cell membranes of mammal species and their content affects a variety of cellular functions. Evidence obtained in animal and human studies suggest that omega-3 PUFA affect many steps of the atherosclerotic process. In blood vessels, omega-3 PUFA improve endothelial function, promote vasodilatation via relaxation of smooth muscle cells, exert antioxidant, antiinflammatory, and antithrombotic actions, delay development of plaques and increase their stability, and decrease wall stiffening. Omega-3 PUFA might affect blood pressure and studies conducted with ambulatory monitoring suggest that supplementation with these fatty acids decreases average 24-hour levels. This effect on blood pressure is related with pretreatment membrane content of omega-3 PUFA and this might explain some inconsistencies among intervention trials. Meta-analyses indicate that omega-3 PUFA have a mild but significant blood pressure lowering effect. While encouraging results were initially obtained with use of omega-3 PUFA supplements in secondary prevention trials, meta-analyses have not confirmed the ability of these fatty acids to decrease the risk of coronary heart and cerebrovascular disease.
Conclusions: Omega-3 PUFA are associated with significant improvement of vascular function and lowering of blood pressure. However, the evidence currently supporting a role of these fatty acids in cardiovascular prevention is weak and needs further investigation
Mineralocorticoid Receptor Antagonists and Clinical Outcomes in Primary Aldosteronism: As Good as Surgery?
No full textPrimary aldosteronism (PA) is detected with increasing frequency in hypertensive patients and is associated with excess cardiovascular, renal, and metabolic complications. For these reasons, appropriate choices for treatment of this endocrine condition are mandatory. Adrenalectomy is safely performed in PA patients when adrenal venous sampling (AVS) demonstrates lateralized aldosterone secretion. AVS, however, is a complex procedure and even among worldwide referral centers there are substantial discrepancies for interpretation of results. Also, in the majority of PA patients with lateralized aldosterone secretion, hypertension may persist after adrenalectomy requiring use of additional antihypertensive agents. Treatment with mineralocorticoid receptor antagonists (MRAs) is currently recommended for PA patients with bilateral adrenal disease, but these agents effectively decrease blood pressure also in patients with unilateral disease, although concern remains for possible sex-related side effects. Prospective studies indicate that MRAs have therapeutic values comparable to surgery in the long-term, inasmuch as they effectively correct metabolic abnormalities and subclinical organ damage and reduce the risk of cardiovascular events and renal disease progression. This article overviews the clinical outcomes obtained in patients with PA with use of MRAs
Long-term renal outcome in patients with primary aldosteronism
No full textContext Experimental animal studies indicate that exposure to increased aldosterone levels might result in renal damage, but the clinical evidence supporting this role of aldosterone is preliminary. Objective To determine the long-term outcome of renal function in patients with primary aldosteronism after surgical or medical treatment. Design, Setting, and Participants Prospective study conducted at an Italian university medical center among a consecutive sample of 50 patients who were diagnosed as having primary aldosteronism between January 1994 and December 2001 and who were followed up for a mean of 6.4 years after treatment with adrenalectomy or spironolactone. Patients with primary aldosteronism were compared with 100 patients with essential hypertension, matched for severity and duration of hypertension. All patients were treated with antihypertensive drugs to reach a target blood pressure of less than 140/90 mm Hg. Main Outcome Measures Primary outcome measures were rates of change of glomerular filtration rate and albuminuria during follow-up. Detection of new-onset microalbuminuria and restoration of normal albumin excretion during follow-up were considered as secondary outcomes. Results At baseline, glomerular filtration rate and albuminuria were higher in patients with primary aldosteronism than those with essential hypertension. The mean blood pressure during the study was 136/81 mm Hg in the primary aldosteronism group and 137/81 mm Hg in the essential hypertension group. Glomerular filtration rate and albuminuria declined during the initial 6-month period in both groups, with a change that was significantly greater ( P <. 001 for both variables) in patients with primary aldosteronism. Subsequent rate of decline of glomerular filtration was comparable in the 2 groups, whereas albuminuria did not progress in the remainder of the follow-up. Restoration of normal albumin excretion from microalbuminuria was significantly more frequent in primary aldosteronism than in essential hypertension ( P=. 02). Conclusion In the majority of patients in this study, primary aldosteronism was characterized by partially reversible renal dysfunction in which elevated albuminuria is a marker of a dynamic rather than structural renal defect
Omega-3 polyunsaturated fatty acids in blood pressure control and essential hypertension
No full textHypertension is a worldwide problem that affects up to 22% of adults and contributes
to the global burden of disability due to cardiovascular disease. Several factors influence
blood pressure and participate to the development of hypertension. Among these
factors, polyunsaturated fatty acids of the omega-3 family (omega-3 PUFA) are effective
hypotensive agents. Through their anti-inflammatory and antioxidant properties,
omega-3 PUFA can improve cardiac hemodynamics and vascular function and
potentially reduce arterial stiffness and atherosclerotic damage. However, despite this
promising evidence many meta-analyses on the cardiovascular effect of omega-3 PUFA
were inconclusive. The choice of the omega-3 PUFA sources, baseline tissue content of
these fatty acids, and individual compliance to their intake can be reasons for such a
discrepancy between studies. Basic and clinical research on these fatty acids documents
interesting mechanisms through which these molecules could be useful in the
treatment of hypertension and its related organ damage. The role of the maternal dietary
habit during pregnancy and the quality of prenatal growth on the effect of omega-3
PUFA in cardiovascular system need further investigations. This chapter summarizes
the literature of the past 30 years on the antihypertensive effects of this family of
essential fatty acids
Serum lipoprotein(a) concentrations and alcohol consumption in hypertension: possible relevance for cardiovascular damage
No full textObjectives To evaluate the relationships between alcohol intake and serum lipoprotein(a) [Lp(a)], a powerful predictor of organ damage, in patients with essential hypertension with a wide range of alcohol intake, and to investigate whether the association between alcohol intake and serum Lp(a) concentrations occurs over the entire spectrum of apo(a) phenotypes. Design Cross-sectional study of a case series. Setting University medical centre. Patients Four hundred and two patients with untreated essential hypertension recruited at a hypertension clinic. Main outcome measures Serum Lp(a) concentrations, apo(a) isoforms, alcohol consumption, smoking habits and cardiovascular status. Results No difference in Lp(a) concentrations was observed between teetotalers and occasional drinkers. Light drinkers (1 -20 g/day ethanol), moderate drinkers (21-50 g/day), and heavy drinkers (>50 g/day) had, respectively, 21, 26 and 57% lower median Lp(a) concentrations than teetotalers and occasional drinkers. Similar findings were obtained when male and female patients were analysed separately. Log Lp(a) concentrations were inversely and independently correlated with alcohol consumption in both men and women with hypertension. The frequency distributions of apo(a) isoforms and liver function parameters were comparable across the different alcohol intake groups. Patients with evidence of cardiovascular damage had greater concentrations of serum Lp(a) and higher frequency of low-molecular weight apo(a) isoforms as compared with patients without such evidence. Conclusions Serum Lp(a) is inversely and dose-dependently related with alcohol intake in patients with hypertension, and this relationship is independent of the size distribution of apo(a) isoforms. Reduction of Lp(a) concentrations by regular consumption of alcohol might favourably affect the atherosclerotic risk profile of patients with hypertension and thereby decrease cardiovascular morbidity
Aldosterone and Left Ventricular Remodeling
No full textExperimental and clinical evidence obtained in the last 2 decades clearly indicates that protracted exposure to inappropriately elevated aldosterone levels causes significant changes in left ventricular structure and function. Animal studies have demonstrated that aldosterone induces myocardial inflammatory changes and fibrosis in the presence of a high salt diet. Moreover, the effects of aldosterone on the heart have been investigated in different clinical conditions. These conditions include systolic and diastolic heart failure, essential hypertension, and primary aldosteronism that offers a unique clinical model to study the cardiac effects of excess aldosterone because these effects are isolated from those of the renin-angiotensin axis. A relatively clear picture is emerging from these studies with regard to aldosterone-related changes in left ventricular mass and geometry. Conversely, no direct effect of aldosterone on left ventricular diastolic function can be demonstrated and improvement of diastolic function obtained in some studies that have employed mineralocorticoid receptor blockers could result from left ventricular mass reduction. Animal experiments demonstrate that effects of aldosterone on the left ventricle require high salt intake to occur, but the evidence of this contribution of salt to aldosterone-induced cardiac changes in humans remains weaker and needs further research. The article reviews the results of clinical studies addressing the role of aldosterone in regulation of LV remodeling and diastolic function, and focuses on the possible relevance of salt intake
Moderate alcohol consumption is associated with left ventricular diastolic dysfunction in nonalcoholic hypertensive patients
No full textEthanol consumption is associated with left ventricular dysfunction in heavy ethanol drinkers. The effect of moderate ethanol intake on left ventricular function in hypertension, however, is unknown. We investigated the relationship between ethanol consumption and cardiac changes in nonalcoholic hypertensive patients. In 335 patients with primary hypertension, we assessed daily ethanol consumption by questionnaires that combined evaluation of recent and lifetime ethanol exposure and examined cardiac structure and function by echocardiography. Patients with abnormal liver tests, previous cardiovascular events, left ventricular ejection fraction <50%, and creatinine clearance <30 mL/min 1.72 m(2) were excluded. Left ventricular hypertrophy was found in 21% of hypertensive patients and diastolic dysfunction was detected in 50% by tissue-Doppler imaging. Ethanol consumption was comparable in hypertensive patients with and without left ventricular hypertrophy, whereas patients with left ventricular diastolic dysfunction had significantly greater consumption than patients with normal ventricular filling. Left atrial diameter, e wave velocity, e/a ratio, and E/e ratio changed progressively with increasing levels of ethanol consumption, and prevalence of left ventricular diastolic dysfunction increased with a change that became statistically significant in patients consuming 20 g/d of ethanol or more. The e wave velocity was inversely correlated with ethanol consumption, and multivariate logistic regression indicated that ethanol consumption predicted diastolic dysfunction independently of age, body mass index, blood pressure, insulin sensitivity, and left ventricular mass index. In conclusion, ethanol consumption is independently associated with left ventricular diastolic dysfunction in nonalcoholic hypertensive patients and might contribute to development of diastolic heart failure
Renal cysts and hypokalemia in primary aldosteronism: results of long-term follow-up after treatment
No full textBackground Cross-sectional studies have reported an elevated prevalence of renal cysts in patients with primary aldosteronism. The nature of this association could be related to hypokalemia and/or hypertension and has never been evaluated in prospective studies. Methods A consecutive sample of 54 patients with tumoral or idiopathic primary aldosteronism was followed after adrenalectomy or treatment with aldosterone antagonists. At baseline, renal cysts were evaluated by renal ultrasound and patients with primary aldosteronism were compared with 323 essential hypertension patients with the same severity and duration of disease, and 113 age- and sex-matched normotensive subjects. Results The adjusted prevalence and average number of renal cysts were significantly greater in patients with primary aldosteronism than in patients with essential hypertension and normotensive subjects. Multivariate analysis revealed that age and plasma potassium levels were independently associated with the presence of renal cysts in patients with primary aldosteronism. Treatment of primary aldosteronism decreased blood pressure ( BP) and restored normal potassium concentrations. After a median follow-up of 6.2 years, no significant change from baseline of cyst number and cyst total volume was observed in patients with both tumoral and idiopathic aldosteronism and in a subset of 100 patients with essential hypertension. In patients with primary aldosteronism, stepwise logistic analysis showed that the presence of renal cysts was associated with worse BP outcome after treatment. Conclusion Renal cystic disease is highly frequent in patients with primary aldosteronism and either surgical or medical treatment halt its progression, supporting the contention that hypokalemia and its severity are the main contributors to cyst formation in these patients
Microalbuminuria and plasma aldosterone levels in nondiabetic treatment-naïve patients with hypertension
No full textOBJECTIVES: Identification of factors that contribute to urinary albumin losses in hypertensive nephropathy is crucial for prevention of renal deterioration. The aim of this study was to investigate the relationship of low-grade albuminuria with plasma aldosterone levels in treatment-naïve hypertensive patients free of additional comorbidities that might affect renal function.
METHODS: In 242 newly diagnosed patients with uncomplicated primary hypertension, we obtained duplicate 24-h urine collections for measurement of urinary albumin/creatinine ratio (UACR) and measured plasma aldosterone levels. Patients with diabetes, overt proteinuria (>300 mg/day), glomerular filtration rate less than 30 ml/min per 1.73 m, and previous renal diseases were excluded.
RESULTS: Increasing UACR was associated with significantly and progressively higher blood pressure (BP), HDL-cholesterol, and plasma aldosterone levels, and with lower glomerular filtration. Microalbuminuria (30-300 mg/day) was detected in 41 (17%) of 242 hypertensive patients, and these patients had significantly higher BP and plasma aldosterone levels (178 ± 113 vs. 128 ± 84 pg/ml; P = 0.001), and lower glomerular filtration than patients without microalbuminuria. UACR was directly and independently correlated with BP and plasma aldosterone levels. In a logistic regression model, presence of microalbuminuria was associated with plasma aldosterone levels independently of glomerular filtration and demographic, anthropometric, and metabolic variables.
CONCLUSION: In nondiabetic, treatment-naïve patients with hypertension, low-grade albuminuria is independently associated with elevated plasma aldosterone. These findings suggest a contribution of aldosterone to the early glomerular changes occurring in hypertensive nephropathy
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