Search PubMed⌕ Search

Biomedical subjects

Gordon H Williams

Publications and source records attributed to Gordon H Williams.

At least 37 records · Page 2Linked to original sources
PubMed2005

Bed rest effects on human calf hemodynamics and orthostatic intolerance: a model-based analysis.

INTRODUCTION: Microgravity-induced orthostatic intolerance continues to be a primary problem after space missions. Its etiology remains uncertain despite significant research efforts over the past years. We hypothesized that calf hemodynamic parameters (compliance and resistance) are significantly affected by 14 to 16-d head-down bed rest (simulated microgravity), and their alterations play a role in the pathogenesis of orthostatic intolerance (OI) following bed rest. METHODS: To estimate these parameters, we developed a model-based approach to quantitatively simulate calf vascular response to venous occlusion, which only necessitates measurement of plethysmography data. In this study, plethysmography data were obtained from 29 subjects before and after 14-16 d of head-down bed rest. The subjects also underwent a tilt/stand test before and after bed rest. RESULTS: Statistical analyses demonstrated an increase in calf compliance (1.87 +/- 0.08, mean +/- SE, pre-bed rest; 2.16 +/- 0.10, end-bed rest) but no significant change in vascular resistance following bed rest. Compared with the tilt-intolerant subjects, those who were tilt-tolerant before bed rest had significantly higher calf compliance [2.00 +/- 0.09 (tolerant); 1.58 +/- 0.09 (intolerant)] and higher vascular resistance [7.79 +/- 0.18 (tolerant); 6.91 +/- 0.40 (intolerant)]. After bed rest, no such difference was detected. DISCUSSION: Based on these results, we validated the hypothesis that, instead of causing orthostatic intolerance, higher calf compliance before bed rest leads to recruitment of compensatory mechanisms (validated by the enhanced vascular resistance during venous occlusion) for a better toleration of orthostatic stress. With the absence of orthostatic challenge during bed rest, the difference in calf hemodynamic parameters is attenuated between the tilt-tolerant and tilt-intolerant groups.

Adaptation, Physiological↗
PubMed2004

Sleep restriction does not affect orthostatic tolerance in the simulated microgravity environment.

Orthostatic intolerance (OI) is a major problem following spaceflight, and, during flight, astronauts also experience sleep restriction. We hypothesized that sleep restriction will compound the risk and severity of OI following simulated microgravity and exaggerate the renal, cardioendocrine, and cardiovascular adaptive responses to it. Nineteen healthy men were equilibrated on a constant diet, after which they underwent a tilt-stand test. They then completed 14-16 days of simulated microgravity [head-down tilt bed rest (HDTB)], followed by repeat tilt-stand test. During HDTB, 11 subjects were assigned to an 8-h sleep protocol (non-sleep restricted), and 8 were assigned to a sleep-restricted protocol with 6 h of sleep per night. During various phases, the following were performed: 24-h urine collections, hormonal measurements, and cardiovascular system identification. Development of presyncope or syncope defined OI. There was a significant decrease in time free of OI (P = 0.02) and an increase in OI occurrence (P = 0.06) after HDTB among all subjects. However, the increase in OI occurrence did not differ significantly between the two groups (P = 0.60). The two groups also experienced similar physiological changes with HDTB (initial increase in sodium excretion; increased excretion of potassium at the end of HDTB; increase in plasma renin activity secretion without a change in serum or urine aldosterone). No significant change in autonomic function or catecholamines was noted. Simulated microgravity leads to increased OI, and sleep restriction does not additively worsen OI in simulated microgravity. Furthermore, conditions of sleep restriction and nonsleep restriction are similar with respect to renal, cardioendocrine, and cardiovascular responses to simulated microgravity.

Adult↗
PubMed2004

Efficacy of eplerenone versus enalapril as monotherapy in systemic hypertension.

This study compared the efficacy and tolerability of eplerenone and enalapril in 499 patients with stage 1 or 2 hypertension who were randomized to receive eplerenone or enalapril for 6 months in a 3-step titration-to-effect study. After 6 months, patients whose diastolic blood pressure (BP) was <90 mm Hg had their dosages down-titrated were followed for an additional 6 months. Diastolic BP was the primary end point. Eplerenone was as effective as enalapril in reducing both systolic BP (eplerenone, -14.5 mm Hg; enalapril, -12.7 mm Hg; p = 0.199) and diastolic BP (eplerenone, -11.2 mm Hg; enalapril, -11.3 mm Hg; p = 0.910) at 6 months. BP reductions at 12 months were also similar between groups (-16.5/-13.3 mm Hg for eplerenone, -14.8/-14.1 mm Hg for enalapril; p = 0.251 and 0.331, respectively). Withdrawal rates for adverse events (eplerenone 7.9%, enalapril 9.3% at 6 months) and treatment failures (eplerenone 23.3%, enalapril 22.8% at 6 months) were also equivalent. Approximately 2/3 of each group had normal BP with monotherapy treatment at 6 months. BP response was independent of renin levels in the eplerenone group, but not in the enalapril group. Both agents reduced albuminuria in patients who had an elevated value at baseline, with significantly greater improvement in patients treated with eplerenone versus enalapril (-61.5% vs -25.7%; p = 0.01). Both agents were similarly well tolerated, and there was no increased incidence of any sexual adverse events in the eplerenone group. Patients taking enalapril had a higher rate of cough. Both agents increased serum potassium levels, but <1% in each group reported adverse events from hyperkalemia. Eplerenone was as effective as enalapril as monotherapy in patients with stage 1 or 2 hypertension, was more effective in reducing albuminuria, and was well tolerated for 12 months.

Adult↗
PubMed2004

Genetic factors associated with volume-sensitive hypertension.

Defining the genetic basis of essential hypertension is most informative when the blood pressure regulation is correlated with physiologic mechanisms, e.g., responses of the renin-angiotensin aldosterone system (RAAS) in hypertensive subjects. The aldosterone response to angiotensin II (Ang II) on a low salt diet is influenced by gender, plasma renin activity, and most significantly, familial resemblance, but only in males and in post-menopausal females. There is familial aggregation of low-renin hypertension, no association with candidate genes of the RAAS, but, a highly significant association with polymorphisms in the alpha-adducin gene. Finally, angiotensinogen (AGT) genotype effects renal and adrenal responses to Ang II in patients with hypertension. These results strongly suggest that in contrast to population-based studies that use hypertension as the phenotype, classifying patients by the variability in physiologic, mechanistic traits enhances the probability of identifying the genetic factors influencing a rise in blood pressure.

Age Factors↗
PubMed2004

Loss of sodium modulation of plasma kinins in human hypertension.

We studied the effect of salt intake and hypertension on the systemic kallikrein-kinin system (KKS), as measured by bradykinin (BK) 1-5, a stable circulating bradykinin metabolite, and the tissue KKS, as measured by urinary kallikrein excretion. Venous BK 1-5, urinary kallikrein, and components of the renin-angiotensin-aldosterone system were measured in 35 normotensive and 19 hypertensive subjects who were maintained on a high (200 mmol/day) or low (10 mmol/day) salt diet. Salt restriction decreased mean arterial pressure (MAP) (P < 0.001 overall) and the plasma angiotensin-converting enzyme (P = 0.017) and increased plasma renin activity (P < 0.001) and serum aldosterone (P < 0.001). There was an interactive effect of salt intake and hypertension on plasma BK 1-5 (P = 0.043), with BK 1-5 significantly lower during low compared with high salt intake in normotensive (24.7 +/- 2.6 versus 34.9 +/- 5.6 fmol/ml, P = 0.002) but not hypertensive subjects (30.6 +/- 4.6 versus 27.5 +/- 2.8 fmol/ml, P = 0.335). In normotensives, the change in plasma BK 1-5 from high to low salt intake correlated with the change in MAP (r = 0.533, P = 0.004). Urinary kallikrein was higher during low compared with high salt intake (P < 0.001) in both groups. There was no effect of salt intake on urinary BK 1-5. In summary, the systemic and renal KKSs act in tandem to modulate the response to salt intake. The systemic system is activated during high salt intake and counterbalances increased vascular response to pressors. With sodium restriction, the renal system is activated and counterbalances the increased sodium-retaining state induced by activation of the renin-angiotensin-aldosterone system. With hypertension, these modulating effects are diminished or lost, supporting a role for both systems in the development/maintenance of hypertension.

Adult↗
PubMed2004

Mineralocorticoid receptor antagonists and hypertension: is there a rationale?

Accumulating evidence indicates that aldosterone is involved in cardiovascular disease by inducing inflammation in the presence of moderate amounts of salt in the diet. Spironolactone and eplerenone are the mineralocorticoid receptor (MR) antagonists currently available for the treatment of hypertension. They have similar safety and antihypertensive efficacy. The advantage of eplerenone is the lower incidence of anti-androgenic and progestational side effects. The rationale for using MR blockade in the treatment of hypertension is threefold: the evidence of antihypertensive efficacy, the phenomenon of "aldosterone escape" occurring with angiotensin-converting enzyme inhibitor and angiotensin-receptor blockade therapy, and the compelling evidence that MR antagonism reduces target-organ damage in hypertensive patients and improves survival in patients with cardiovascular disease. Thus, blockade of the MR may be very useful in many patients with hypertension, particularly those at risk for or having evidence of target-organ damage.

Albuminuria↗
PubMed2004

Process irregularity of cortisol and adrenocorticotropin secretion in men with major depressive disorder.

Although evidence suggests that major depressive disorder (MDD) is associated with hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis, research on basal HPA axis hormone levels in MDD patients has been inconclusive. Definitive characterization of basal cortisol and adrenocorticotropin (ACTH) secretion may be important for understanding the pathophysiology of this disorder. In recent years, a new approach to the analysis of basal hormone secretion has been developed involving the approximate entropy (ApEn) statistic, which represents the degree of disorderliness or serial irregularity in a time series of hormone levels. ApEn has been shown to reflect the degree of coordination in integrated network systems and has provided new insights into the pathophysiology of a number of endocrine conditions. In the study reported here, 15 medication-free men with MDD and 15 healthy control men were admitted to a General Clinical Research Center and had blood sampled for cortisol and ACTH determinations every hour over a 24-h period. The cortisol and ACTH time series were characterized with a cosinor analysis and with analysis of ApEn. Depressed patients and control subjects did not differ significantly on any parameter derived from the cosinor analysis or on several other standard indices of basal hormone secretion. However, the depressed men had significantly increased cortisol ApEn and significantly decreased ACTH ApEn compared with the healthy subjects. The ApEn findings suggest a loss of regulatory control over cortisol secretion, and possibly increased cortisol feedback on the pituitary in the depressed patients. Together, these results are most consistent with a primary abnormality of the adrenal gland and suggest that further investigation of adrenal gland physiology may be informative for the pathophysiology of depression.

Adrenocorticotropic Hormone↗
PubMed2004

Effects of conjugated oestrogen and droloxifene on the renin-angiotensin system, blood pressure and renal blood flow in postmenopausal women.

OBJECTIVE: The aim of this study was to evaluate the effect of conjugated equine oestrogen (CEE), and droloxifene, a selective oestrogen receptor modulator (SERM) on individual components of renin-angiotensin-aldosterone (RAAS) and blood pressure (BP) in postmenopausal women. DESIGN AND PATIENTS: Twenty-one normotensive (NT) and 10 hypertensive (HT) postmenopausal women received either CEE (0.625 mg/day) or droloxifene (60 mg/day) for 6 weeks and, after a 4-week washout, were restudied on the alternate medication. MEASUREMENTS: Hormones of the RAAS and supine BP were measured prior to and at the end of each drug treatment in all subjects. In a subgroup of the NT (n = 10), 24 h ambulatory BP was performed and renal blood flow was determined by PAH clearance both basally and in response to 45-min angiotensin II (Ang II) infusion (3 ng/kg/min). RESULTS: CEE significantly increased angiotensinogen, decreased active renin and angiotensin-converting enzyme (ACE), and maintained plasma immunoreactive (ir) angiotensin I (Ang I) levels compared to baseline. With droloxifene, angiotensinogen, active renin and Ang I remained unchanged. Both CEE and droloxifene significantly increased plasma ir-Ang II levels (pmol/l) in NT (baseline: 25.7 +/- 2.5, CEE: 36.6 +/- 3.4, droloxifene: 33.3 +/- 3.1, P < 0.002) and HT women (baseline: 17.9 +/- 2.3, CEE: 27.9 +/- 3.2, droloxifene: 25.9 +/- 4.9, P < 0.005). Renal blood flow was lower on CEE (P = 0.02) compared with baseline. Systemic BP (supine and 24-h ambulatory) was unchanged during both treatments. CONCLUSION: This study demonstrates higher circulating levels of ir-Ang II with CEE and droloxifene.

Aged↗
PubMed2004

Plasma aldosterone concentration in the patient with diabetes mellitus.

BACKGROUND: Vascular injury at the microvascular and macrovascular levels plays a crucial role in the patient with diabetes mellitus. Evidence for renin-system activation in many patients with type 1 diabetes mellitus has raised the possibility that aldosterone-widely recognized as a contributor to vascular injury-could play a role. METHODS: We examined the state of the renin-angiotensin-aldosterone system (RAAS) in 58 subjects with type 1 diabetes mellitus and 64 age-matched normal control subjects. All studies were performed on a fixed sodium (200 mmol/day) and potassium (100 mmol/day intake), and samples were drawn at 8:00 a.m. to avoid the influence of circadian rhythms. RESULTS: The patient with diabetes mellitus showed an increase in plasma renin activity (PRA) (P < 0.01), plasma angiotensin II concentration (P < 0.01), and plasma aldosterone concentration (P < 0.001). A striking influence of the angiotensin receptor blocker, candesartan, on plasma aldosterone concentration in the patients with diabetes mellitus suggested strongly that renin-system activation is responsible for the elevated plasma aldosterone concentration. CONCLUSION: Pharmacologic interruption of the effects of aldosterone at the tissue level could be especially useful in patients with diabetes mellitus. The dose of agents that block the renin-angiotensin system (RAS) should be adjusted to maximize the fall in plasma aldosterone concentration.

Adolescent↗
PubMed2004

Uric acid and the state of the intrarenal renin-angiotensin system in humans.

BACKGROUND: Experimental hyperuricemia is marked by an activated intrarenal renin-angiotensin system (RAS). The renal vascular response to exogenous angiotensin II (Ang II) provides an indirect measure of intrarenal RAS activity. We tested the hypothesis that the serum uric acid concentration predicts the renal vascular response to Ang II. METHODS: A total of 249 subjects in high sodium balance had the renal plasma flow (RPF) response to Ang II measured. Para-aminohippuric acid (PAH) clearance was used to estimate RPF. Multivariable regression analysis determined if the serum uric acid concentration independently predicts the RPF response to Ang II. Variables considered included age, gender, race, body mass index (BMI), hypertension status, blood pressure, basal RPF, creatinine clearance, serum insulin, serum glucose, serum high-density lipoprotein (HDL), serum triglycerides, and plasma renin activity (PRA). RESULTS: Uric acid concentration negatively correlated with the RPF response to Ang II (r=-0.37, P < 0.001). In univariate analysis, age, BMI, hypertension, triglycerides, and blood pressure were negatively associated, and basal RPF, HDL, and female gender were positively associated with the RPF response to Ang II. In multivariable analysis, serum uric acid concentration independently predicted the RPF response to Ang II (beta=-5.3, P < 0.001). CONCLUSION: Serum uric acid independently predicted blunted renal vascular responsiveness to Ang II, consistent with results from experimental hyperuricemia showing an activated intrarenal RAS. This could be due to a direct effect of uric acid or reflect a more fundamental renal process. These data may have relevance to the association of uric acid with risk for hypertension and nephropathy.

Adult↗
PubMed2004

Renal, endocrine, and cardiovascular responses to bed rest in male subjects on a constant diet.

BACKGROUND: Exposure to actual and simulated microgravity induces cardiovascular deconditioning through a variety of factors. Although the mechanisms involved remain uncertain, one involves alterations in volume-regulating systems--the hypothesis being tested in this study. To maximize our ability to detect subtle changes in the volume-regulating systems, subjects were studied on a high-average salt intake to maximally suppress these systems basally. METHODS: Fourteen healthy male subjects underwent 14-day head-down tilt bed rest (HDTB) during which a constant 200 mEq sodium, 100 mEq potassium diet was maintained. Daily 24-hour urine collection was performed; plasma renin activity, serum aldosterone, plethysmography, and cardiovascular system identification were performed during a control period (pre-HDTB) and at the end of HDTB (end HDTB). RESULTS: Sodium excretion increased initially (pre-HDTB = 182.8 +/- 10.4 mEq/total volume; early HDTB = 236.4 +/- 13.0; p = .002) and then returned to baseline values. Potassium excretion increased 4 days after the initiation of HDTB and remained elevated thereafter (pre-HDTB = 82.2 +/- 2.4/total volume; mid- to late HDTB = 89.4 +/- 2.1; p = .02). Plasma renin activity increased significantly with HDTB (pre-HDTB = 1.28 +/- 0.21 ng/mL/h; end HDTB = 1.69 +/- 0.18; p = .01), but serum aldosterone did not change. A significant decrease in autonomic responsiveness and an increase in leg compliance were observed. CONCLUSIONS: We conclude that even in the presence of a high-average salt intake diet, simulated microgravity leads to renal, cardioendocrine, and cardiovascular system alterations that likely contribute to cardiovascular deconditioning.

Adult↗
PubMed2004

Thyroid function and blood pressure homeostasis in euthyroid subjects.

Overt and subclinical hypothyroidism are associated with increased systemic vascular resistance and hypertension. We examined the relationship between thyroid function and blood pressure homeostasis in euthyroid individuals. A total of 284 subjects (68% hypertensive) consumed high- (200 mmol) and low- (10 mmol) sodium diets, and their blood pressure responses were assessed as percentage change in the mean arterial pressure (MAP). p-Aminohippuric acid clearance was used to estimate effective renal plasma flow. Renal vascular resistance (RVR) was calculated as MAP divided by effective renal plasma flow. Serum free T(4) index (FTI) was lower (P < 0.0001) and TSH was higher (P = 0.046) in hypertensive compared with normotensive subjects independent of other baseline characteristics. FTI (beta = -1.51, P < 0.0001), baseline MAP, and race independently predicted MAP salt sensitivity. The FTI relationship with salt sensitivity adjusted for baseline MAP and race was similar among normotensive (beta = -1.42, P = 0.008) and hypertensive subjects (beta = -1.66, P = 0.0001). FTI correlated negatively with high- (P = 0.0001) and low- (P = 0.008) salt RVR, whereas TSH correlated positively with high- (P = 0.016) and low- (P = 0.012) salt RVR independent of age, gender, race, and body mass index. We have found that FTI is lower and TSH is higher in hypertensive compared with normotensive euthyroid subjects and that FTI independently predicts blood pressure salt sensitivity. These data show that the influence of thyroid function on blood pressure homeostasis extends into euthyroid range and likely reflects the action of thyroid hormone on peripheral vasculature.

Adult↗
PubMed2003

Diurnal variation of aldosterone and plasma renin activity: timing relation to melatonin and cortisol and consistency after prolonged bed rest.

Exposure to prolonged bed rest is known to induce changes in the renin-angiotensin-aldosterone system (RAAS) by way of posture, sodium and potassium balance, and stress, which may have serious consequences for patients. We focused on the diurnal variation of the RAAS by investigating changes in the levels of plasma renin activity (PRA) and aldosterone; for comparison to markers of the intrinsic pacemaker and to stress, we measured melatonin and cortisol. PRA, aldosterone, melatonin, and cortisol were measured hourly in 10 normal subjects with standardized sleep patterns, posture, and diet at baseline and after 11 days of prolonged bed rest conducted under a light-dark cycle. Circadian characteristics of hormone secretion patterns were estimated by multiple harmonic regression with excellent goodness-of-fit measures. Variability in the melatonin and cortisol patterns across subjects was minimal. Even for pulsatile hormones, this technique successfully estimated the acrophase, which was the salient feature. Baseline hormone peak times started with melatonin near the middle of the sleep period, followed by PRA, then aldosterone, and then cortisol around wake time. Prolonged bed rest did not induce significant changes in any timing characteristic of the secretion patterns. Baseline and prolonged bed rest peak times for melatonin and cortisol and amplitude characteristics for all hormones were highly correlated, indicating consistency within individuals. These data provide strong evidence that prolonged bed rest of 11 days' duration does not disrupt either the timing characteristics of the RAAS or the intrinsic pacemaker.

Adult↗
PubMed2003

Genetic determinants of nonmodulating hypertension.

We sought to determine whether genes of the renin-angiotensin-aldosterone system can predict the nonmodulating intermediate phenotype in essential hypertension. Aldosterone responses to angiotensin II were assessed in 298 subjects with hypertension. Subjects were genotyped at the angiotensinogen M235T, angiotensin-converting enzyme I/D, aldosterone synthase C-344 T, renin, angiotensin II type 1 receptor, and adducin loci. The data were analyzed by Student t test, ANOVA, stepwise linear regression and general linear model or GENMOD regression techniques, and chi2 analysis odds ratios (ORs). Aldosterone response varied by genotype for angiotensin and aldosterone synthase but not for the other loci. The combination of angiotensinogen 235 TT and angiotensin-converting enzyme DD showed further reduction (P=0.0377) when compared with angiotensinogen 235 TT alone, an example of genetic epistasis. When the subject was required also to possess the CYP11B2 -344 TT genotype, there was a further substantial reduction. Of these 3 loci, only angiotensinogen 235 TT significantly increased the OR of predicting the nonmodulating hypertensive phenotype (OR, 2.00; 95% confidence interval, 1.152 to 3.51). However, when angiotensin-converting enzyme DD was combined with angiotensinogen 235 TT, the OR nearly doubled to 3.74, with a further increase to 5.36-fold when the subject possessed all 3 genotypes. Thus, the angiotensinogen, angiotensin-converting enzyme, and aldosterone synthase genotypes identified individuals with the nonmodulating phenotype with an increasing degree of fidelity. For this subclass of essential hypertension, it is likely that genotyping can be substituted for complex phenotyping for therapeutic and preventive decision making.

Age Factors↗
PubMed2003

Acute angiotensin II increases plasma F2-isoprostanes in salt-replete human hypertensives.

Angiotensin (Ang) II induces oxidative stress in vitro and in animal models of hypertension. We tested the hypothesis that Ang II increases oxidative stress in human hypertension, as assessed by plasma F2-isoprostane concentrations. Plasma F2-isoprostanes, hemodynamic and endocrine parameters were measured at baseline and following a 55 min infusion of 3 ng/kg/min Ang II in 13 normotensive and 13 hypertensive volunteers ingesting a high- (200 mmol/d) or low- (10 mmol/d) sodium diet. Mean arterial pressure (MAP) and body mass index were higher in hypertensive subjects. Ang II infusion increased MAP (p<.001) and plasma aldosterone concentrations (p<.001) and decreased plasma renin activity (p<.001) and renal plasma flow (p<.001) to a similar extent in both groups. Plasma F2-isoprostane concentrations were similar at baseline. There was no effect of Ang II on F2-isoprostane concentrations during low-salt intake in either group (normotensive 51.7 +/- 7.1 to 53.7 +/- 6.5 pg/ml and hypertensive 52.2 +/- 8.2 to 56.2 +/- 10.0 pg/ml; mean +/- SE). During high-salt intake, Ang II increased F2-isoprostane concentrations in the hypertensive group (52.3 +/- 7.2 to 63.2 +/- 10.4 pg/ml, p=0.010) but not in the normotensive group (54.2 +/- 4.4 to 58.9 +/- 6.6 pg/ml, p=0.83). Acute Ang II infusion increases oxidative stress in vivo in hypertensive humans. The renin-angiotensin system may contribute to oxidative stress in human cardiovascular disease.

Adult↗
PubMed2003

Effects of eplerenone, enalapril, and eplerenone/enalapril in patients with essential hypertension and left ventricular hypertrophy: the 4E-left ventricular hypertrophy study.

BACKGROUND: Elevated renin-angiotensin-aldosterone system activity correlates with left ventricular hypertrophy (LVH) and cardiovascular risk, but the relative contributions of angiotensin II and aldosterone remain unclear. This study compared LVH regression during treatment with the selective aldosterone blocker eplerenone, enalapril, and their combination in patients with hypertension. METHODS AND RESULTS: A 9-month, double-blind, randomized study was performed in 202 patients with LVH and hypertension who received eplerenone 200 mg daily, enalapril 40 mg daily, or eplerenone 200 mg and enalapril 10 mg daily. At week 8, hydrochlorothiazide 12.5 to 25 mg and/or amlodipine 10 mg was added if diastolic blood pressure was >90 mm Hg. Change in left ventricular (LV) mass as assessed by MRI was the primary end point. Change in blood pressure, renin-angiotensin-aldosterone system hormones, albuminuria, and safety were also assessed. Eplerenone significantly reduced LV mass from baseline (-14.5+/-3.36 g; n=50) similarly to enalapril (-19.7+/-3.20 g; n=54; P=0.258), but eplerenone/enalapril (-27.2+/-3.39 g; n=49) was more effective than eplerenone alone (P=0.007). All treatments reduced systolic blood pressure and diastolic blood pressure from baseline (eplerenone, -23.8 and -11.9 mm Hg; enalapril, -24.7 and -13.4 mm Hg; and eplerenone/enalapril, -28.7 and -14.4 mm Hg, P=0.048, in systolic blood pressure compared with eplerenone alone). Cough was more common with enalapril than with eplerenone (P=0.033), and elevated potassium was more common with eplerenone. CONCLUSIONS: Eplerenone was as effective as enalapril in LVH regression and blood pressure control. The combination of eplerenone and enalapril was more effective in reducing LV mass and systolic blood pressure than eplerenone alone.

Adult↗
PubMed2003

Effects of simulated microgravity on closed-loop cardiovascular regulation and orthostatic intolerance: analysis by means of system identification.

Microgravity-induced orthostatic intolerance (OI) continues to be a primary concern for the human space program. To test the hypothesis that exposure to simulated microgravity significantly alters autonomic nervous control and, thus, contributes to increased incidence of OI, we employed the cardiovascular system identification (CSI) technique to evaluate quantitatively parasympathetic and sympathetic regulation of heart rate (HR). The CSI method analyzes second-to-second fluctuations in noninvasively measured HR, arterial blood pressure, and instantaneous lung volume. The coupling mechanisms between these signals are characterized by using a closed-loop model. Parameters reflecting parasympathetic and sympathetic responsiveness with regard to HR regulation can be extracted from the identified coupling mechanisms. We analyzed data collected from 29 human subjects before and after 16 days of head-down-tilt bed rest (simulated microgravity). Statistical analyses showed that parasympathetic and sympathetic responsiveness was impaired by bed rest. A lower sympathetic responsiveness and a higher parasympathetic responsiveness measured before bed rest identified individuals at greater risk of OI before and after bed rest. We propose an algorithm to predict OI after bed rest from measures obtained before bed rest.

Adult↗