Female sex hormones, salt, and blood pressure regulation

There are gender-associated differences in blood pressure (BP) in humans, with men having higher BP than age-matched pre-menopausal women and being at greater risk for cardiovascular and renal diseases. The mechanisms responsible for the gender differences in BP control and regulation are not clear, although there is some evidence that interactions between sex hormones and the kidneys could play a role. However, the response to salt in pre- and post-menopausal women, and in particular the influence of exogenous and endogenous female sex hormones on renal hemodynamics and tubular segmental sodium handling, have been poorly investigated. Recently we have shown that both endogenous and exogenous female sex hormones markedly influence the systemic and renal hemodynamic response to salt. We have found that BP in young normotensive women, regardless of oral contraceptive use, is rather insensitive to salt. However, the renal hemodynamic and the tubular responses to salt vary significantly during the normal menstrual cycle and with the administration of oral contraceptives. Furthermore, after the menopause, BP tends to become salt sensitive, a pattern that could be due to aging as well as to the modification of the sex hormone profile. These observations provide new insights pertaining to potential mechanisms explaining the lower incidence of cardiovascular disease and progression of renal disease in pre-menopausal women (which tend to disappear with the menopause); these observations also emphasize the importance of considering more carefully the phase of the menstrual cycle whenever conducting physiologic studies in women and enrolling women in clinical studies. Finally, increased salt sensitivity in menopausal women strongly encourages the use of diuretics

Effects of the peroxisome proliferator-activated receptor (PPAR)-γ agonist pioglitazone on renal and hormonal responses to salt in diabetic and hypertensive individuals

Aims/hypothesis: Glitazones are powerful insulin sensitisers prescribed for the treatment of type 2 diabetes. Their use is, however, associated with fluid retention and an increased risk of congestive heart failure. We previously demonstrated that pioglitazone increases proximal sodium reabsorption in healthy volunteers. This study examines the effects of pioglitazone on renal sodium handling in individuals prone to insulin resistance, i.e. those with diabetes and/or hypertension. Methods: In this double-blind randomised placebo-controlled four-way crossover study, we examined the effects of pioglitazone (45mg daily during 6weeks) or placebo on renal, systemic and hormonal responses to changes in sodium intake in 16 individuals, eight with type 2 diabetes and eight with hypertension. Results: Pioglitazone was associated with a rapid increase in body weight and an increase in diurnal proximal sodium reabsorption, without any change in renal haemodynamics or in the modulation of the renin-angiotensin aldosterone system to changes in salt intake. A compensatory increase in brain natriuretic peptide levels was observed. In spite of sodium retention, pioglitazone dissociated the blood-pressure response to salt and abolished salt sensitivity in salt-sensitive individuals. Conclusions/interpretation: Pioglitazone increases diurnal proximal sodium retention in diabetic and hypertensive individuals. These effects cause fluid retention and may contribute to the increased incidence of congestive heart failure with glitazones. Trial registration:: ClinicalTrial.gov NCT01090752 Funding:: Hypertension Research Foundation Lausann

Increased Cardiovascular Reactivity to Acute Stress and Salt-Loading in Adult Male Offspring of Fat Fed Non-Obese Rats

Diet-induced obesity in rat pregnancy has been shown previously to be associated with consistently raised blood pressure in the offspring, attributed to sympathetic over-activation, but the relative contributions to this phenotype of maternal obesity versus raised dietary fat is unknown. Sprague-Dawley female rats were fed either a control (4.3% fat, n = 11) or lard-enriched (23.6% fat, n = 16) chow 10 days prior to mating, throughout pregnancy and lactation. In conscious adult (9-month-old) offspring cardiovascular parameters were measured (radiotelemetry). The short period of fat-feeding did not increase maternal weight versus controls and the baseline blood pressure was similar in offspring of fat fed dams (OF) and controls (OC). However, adult male OF showed heightened cardiovascular reactivity to acute restraint stress (p<0.01; Δ systolic blood pressure (SBP) and Δheart rate (HR)) with a prolonged recovery time compared to male OC. α1/β-adrenergic receptor blockade normalised the response. Also, after dietary salt-loading (8%-NaCl ad libitum for 1 week) male OF demonstrated higher SBP (p<0.05) in the awake phase (night-time) and increased low/high frequency ratio of power spectral density of HR variability versus OC. Baroreflex gain and basal power spectral density components of the heart rate or blood pressure were similar in male OF and OC. Minor abnormalities were evident in female OF. Fat feeding in the absence of maternal obesity in pregnant rats leads to altered sympathetic control of cardiovascular function in adult male offspring, and hypertension in response to stressor stimuli

Manifestations renales des affections virales. [Renal manifestations of viral diseases]

Like bacterial diseases viral diseases may also be accompanied by functional renal disorders or abnormalities of the urinary sediment. Thus, to find a hematuria or an isolated proteinuria in the context of influenza or hepatitis is not rare at all. In certain cases viral affections may even be accompanied by a nephrotic syndrome. This article aims at the discussion of multiple renal disorders appearing in the context of hepatitis B and C and AIDS

Gonadal steroids, salt-sensitivity and renal function

PURPOSE OF REVIEW: The aim of this article is to discuss the impact of male and female sex hormones on renal function and to develop the concept that salt-sensitivity of renal function behaves independently of the systemic blood pressure response to salt and may contribute to renal sex-specific differences. RECENT FINDINGS: Men exhibit a more rapid age-related decline in renal function than women and some renal diseases are clearly sex dependent. Recent studies have shown that gonadal steroids have an important influence on sodium handling and renal hemodynamics that may offer a key for understanding the sexual dimorphism of the renal function. It has been found that androgens increase proximal sodium reabsorption and intraglomerular pressure by modulating afferent and efferent arteriolar tonus via angiotensin II, endothelin and oxidative stress. In contrast, female sex hormones lead to a renal vasodilation and decrease filtration fraction. SUMMARY: Some newly discovered mechanisms triggering the salt-sensitivity of the renal function and the interaction between gonadal steroids and components of the renin cascade may play an important role in the dimorphism of renal response to salt

[Does constitutional hypotension exist?]

Orthostatic hypotension is frequently related to severe insufficiency of the autonomic nervous system associated with neuropathy or systemic disease like diabetes. Inversely, pre-syncopal orthostatic symptoms associated with mild drop in orthostatic blood pressure is quite often a reason to seek medical care, but is relatively unrecognized in the literature. Recently a syndrome of mild orthostatic intolerance has been defined, and seem to be quite common among young subjects, characterized by frequent orthostatic presyncopal symptoms associated with orthostatic tachycardia and high plasma catecholamines levels. In the paper, we will review different causes of orthostatic hypotension, and mention some physiopathological mechanisms linked to renal sodium handling. In particular, alterations in renal proximal segmental handling of sodium might generate and play a pathophysiological role in maintenance of the orthostatic hypotension. Finally, we will evoke some therapeutical aspects

Reasons for not intensifying antihypertensive treatment (RIAT): a primary care antihypertensive intervention study

OBJECTIVE: Hypertension is often poorly controlled, despite its importance and despite the availability of very effective treatments. An under-recognized problem is the failure of consensus guidelines to acknowledge the important difference between efficacy in clinical trials and effectiveness in clinical practice. The present survey was designed to prospectively assess what is the target blood pressure (BP) goal defined by a general practitioner (GP) for an individual patient, and what are the reasons for not modifying an antihypertensive drug regimen, when pre-defined individual BP goals are not achieved. DESIGN: Family practice based, open intervention survey. SUBJECTS: Participating GPs enrolled 2621 hypertensive patients. At the first visit each physician was required to assess the cardiovascular risk profile of each patient and to define individual BP targets. INTERVENTIONS: Treatment was started with irbesartan alone or in fixed combination with hydrochlorothiazide. Follow-up visits were suggested after 1 month, 2 months and 4 months. Physicians were asked to report BP values under the new treatment regimen and to indicate whether in their opinion pre-defined BP targets set at baseline were achieved or not and whether the antihypertensive regimen was modified or maintained in relation to whether target BP was reached or not. MAIN OUTCOME MEASURE: To provide reasons for not changing the treatment even though BP goals were missed. RESULTS: Average target BP values defined by the physicians at baseline were 138 +/- 8 mmHg for systolic and 84 +/- 5 mmHg for diastolic BP. Among GPs, defined target BP values did not depend on individual risk stratification, but rather depended on baseline BP values. At baseline systolic and diastolic BP averaged 165/97 +/- 17/10 mmHg, while at the last visit achieved BP averaged 140/84 +/- 14/8 mmHg. There were three main reasons for not intensifying antihypertensive treatment when BP targets were not achieved. These reasons were: (1). the assumption that the time after starting the new drug was too short to appreciate its full effect (44% at first, 14% at last follow-up), (2). that there was a clear improvement or the target BP was almost reached (24% at first, 34% at last follow-up) or (3). that self-measurements were considered satisfactorily (10% at the last visit). CONCLUSIONS: Failure of physicians to follow guidelines is apparently dependent on the belief that baseline BP dictates the target, that a clear improvement in BP might be sufficient and that the full drug effect may take up to 4 months or more to be attained

Sinistrin clearance for determination of glomerular filtration rate: a reappraisal of various approaches using a new analytical method

Several approaches are available to estimate the glomerular filtration rate (GFR) from the sinistrin clearance. To compare such approaches, GFR was estimated in six healthy volunteers, both after a bolus injection and a bolus dose followed by a 6-hour infusion. A recently developed high-performance liquid chromatography method was used for the determination of sinistrin levels, enabling precise measurements in plasma and urine samples with high sensitivity. Blood and urine were sampled up to 6 hours. Four calculation methods for estimating GFR were applied: 1) classical ratio of urinary excretion rate over plasma concentration (UV/P); 2) two-point (log-linear regression slope times monocompartmental volume of distribution) after bolus; 3) ratio of dose over area under the curve (D/AUC) after bolus; and 4) ratio of infusion rate over steady-state concentration during infusion (Rinf/P). The results obtained by fitting a pharmacokinetic model to all the plasma and urine data served as the standard against which the performance of the respective calculation methods were examined. The UV/P method performed poorly on bolus data, mainly by underestimating GFR at late times; on both bolus and infusion data, it suffered from important imprecisions on the urinary volume. The two-point method appeared applicable only between 2 and 4 hours after the bolus dose. The D/AUC method with extrapolation to infinity was highly reliable when integrating the concentrations up to 3 hours or more after the bolus dose. The Rinf/P method was satisfactory if applied later than 2 to 3 hours after the loading dose. The advantages and drawbacks of each method have to be evaluated in relation to the particular clinical setting in which GFR is to be estimated

Renal sodium handling in patients with normal pressure glaucoma.

Low BP (blood pressure) is a recognized risk factor for some patients with NPG (normal pressure glaucoma). We have shown previously that patients with orthostasis have impaired circadian renal handling of sodium, which may contribute to the low BP. Therefore the aim of the present study was to examine the renal handling of sodium, the circadian variations in BP and the neurohormonal response to an orthostatic test in a selected subpopulation of 18 patients with NPG with vasospastic and orthostatic symptoms, and in 24 healthy control subjects. The variations in BP and renal tubular sodium handling were evaluated using 24 h ambulatory BP recordings, 24 h urine collections and determination of endogenous lithium clearance as a marker of proximal sodium reabsorption. The neurohormonal and BP responses to changes in posture were also determined in a 30 min orthostatic test. This selected group of patients with NPG had lower 24 h ambulatory BPs (P&amp;lt;0.001), and a more pronounced fall in BP when assuming an upright position (P&amp;lt;0.001) compared with controls. FE(Li) (fractional excretion of lithium) was higher in patients with NPG than controls during the day (36.6+/-21.8 compared with 20.4+/-8.7% respectively; P&amp;lt;0.01; values are means+/-S.D.) as well as during the night (38.8+/-41.9 compared with 19.7+/-10.8% respectively; P&amp;lt;0.02), suggesting a reduced reabsorption of sodium in the proximal tubule. This was compensated for by an increased distal reabsorption of sodium in patients with NPG (P&amp;lt;0.01). These data demonstrate that patients with vasospastic NPG have a high excretion of lithium, suggesting reduced sodium reabsorption in the proximal tubule, in spite of a low BP. The abnormal renal sodium handling might contribute to the maintenance of arterial hypotension and progression of the optic nerve damage in these patients