Dietary sodium and nocturnal blood pressure dipping in normotensive men and women.

Impaired nocturnal blood pressure (BP) dipping (i.e., <10% decline in nocturnal BP) is associated with an increased risk of cerebrovascular and cardiovascular diseases. Excess sodium has been shown to impair BP regulation and increase cardiovascular disease risk, yet few studies have assessed the influence of dietary sodium on nocturnal dipping in normotensive adults. The purpose of this study was to determine the effects of dietary sodium on BP dipping in normotensive men and women. Eighty healthy normotensive adults participated in a controlled feeding study (men: n=39, 34±2 years; women: n=41, 41±2 years). Participants consumed a standardized run-in 100 mmol sodium per day diet for 7 days, followed by 7 days of low-sodium (LS; 20 mmol per day) and high-sodium (HS; 300 mmol per day) diets in random order. On the final day of each diet, subjects wore a 24 h ambulatory BP monitor, collected a 24 h urine sample and provided a blood sample. During the run-in diet, 24 h urinary sodium excretion was 79.4±5.1 mmol per 24 h in men and 85.3±5.5 mmol per 24 h in women (P>0.05). Systolic BP dipping was not different between men (11.4±1.0%) and women (11.2±0.9%); (P>0.05). During the HS diet, 24 h urinary sodium excretion increased compared with the LS diet in men (LS=31.7±4.6 mmol per 24 h vs HS=235.0±13.9 mmol per 24 h, P<0.01) and women (LS=25.8±2.2 mmol per 24 h vs HS=234.7±13.8 mmol per 24 h, P<0.01). Despite this large increase in sodium intake and excretion, systolic BP dipping was not blunted in men (LS=8.9±1.0% vs HS=9.4±1.2%, P>0.05) or women (LS=10.3±0.8% vs HS=10.5±0.8%, P>0.05). Among normotensive men and women, HS does not blunt nocturnal BP dipping.

Rapid onset pressor and sympathetic responses to static handgrip in older hypertensive adults.

Exaggerated pressor and muscle sympathetic nerve activity (MSNA) responses have been reported during static handgrip in hypertensive (HTN) adults. Recent work suggests that such responses may occur much more rapidly in HTN patients; however, this has not been extensively studied. Thus, we examined the blood pressure (BP) and MSNA responses at the immediate onset of muscle contraction and tested the hypothesis that older HTN adults would exhibit rapid onset pressor and sympathetic responses compared with normotensive (NTN) adults. Heart rate (HR), BP (Finometer) and MSNA (peroneal microneurography) were retrospectively analyzed in 15 HTN (62 ± 1 years; resting BP 153 ± 3/91 ± 5 mm Hg) and 23 age-matched NTN (60 ± 1 years; resting BP 112 ± 1/67 ± 2 mm Hg) subjects during the first 30 s of static handgrip at 30 and 40% of maximal voluntary contraction (MVC). HTN adults demonstrated exaggerated increases in mean BP during the first 10 s of both 30% (NTN: Δ1 ± 1 vs HTN: Δ7 ± 2 mm Hg; P < 0.05) and 40% (NTN: Δ2 ± 1 vs HTN: Δ8 ± 2 mm Hg; P < 0.05) intensity handgrip. Likewise, HTN adults exhibited atypical increases in MSNA within 10 s. Increases in HR were also greater in HTN adults at 10 s of 30% MVC handgrip, although not at 40% MVC. There were no group differences in 10 s pressor or sympathetic responses to a cold pressor test, suggesting no differences in generalized sympathetic responsiveness. Thus, static handgrip evokes rapid onset pressor and sympathetic responses in older HTN adults. These findings suggest that older HTN adults likely have greater cardiovascular risk even during short duration activities of daily living that contain an isometric component.

Neuromechanical coupling in the regulation of muscle tone and joint stiffness.

The ability of the nervous system to accommodate changes to joint mechanics is crucial in the maintenance of joint stability and the prevention of injury. This neuromechanical coupling is achieved through several mechanisms such as the central and peripheral regulation of muscle tone and subsequent alterations to joint stiffness. Following joint injury, such as a ligamentous sprains, some patients develop functional instability or require surgery to stabilize the joint, while others are able to cope and display limited impairments. Several researchers have attempted to explain these divergent outcomes, although research using proprioceptive tasks and quantifying reaction times has led to equivocal results. Recent innovations have allowed for the simultaneous measurement of mechanical and nervous system function among these subsets. The intent of this review was to explore the relationships between joint stiffness and nervous system function, and how it changes following injury. By better understanding these mechanisms, researchers and clinicians may better develop and implement rehabilitation protocols to target individual deficits among injured populations.

Salt loading has a more deleterious effect on flow-mediated dilation in salt-resistant men than women.

BACKGROUND AND AIMS: Dietary sodium loading has been shown to adversely impact endothelial function independently of blood pressure (BP). However, it is unknown whether dietary sodium loading impacts endothelial function differently in men as compared to women. The aim of this study was to test the hypothesis that endothelial-dependent dilation (EDD) would be lower in men as compared to women in response to a high sodium diet. METHODS AND RESULTS: Thirty subjects (14F, 31±2y; 16M, 29±2y) underwent a randomized, crossover, controlled diet study consisting of 7 days of low sodium (LS; 20 mmol/day) and 7 days of high sodium (HS; 300-350 mmol/day). Salt-resistance was determined by a change in 24-hr mean arterial pressure (MAP) ≤ 5 mm Hg between HS and LS as assessed on day 7 of each diet. Blood and 24-hr urine were also collected and EDD was assessed by brachial artery flow-mediated dilation (FMD). By design, MAP was not different between LS and HS conditions and urinary sodium excretion increased on HS diet (P < 0.01). FMD did not differ between men and women on the LS diet (10.2 ± 0.65 vs. 10.7 ± 0.83; P > 0.05) and declined in both men and women on HS (P < 0.001). However, FMD was lower in men as compared to women on HS (5.7 ± 0.5 vs. 8.6 ± 0.86; P < 0.01). CONCLUSIONS: HS reduced FMD in both men and women. In response to an HS diet, FMD was lower in men compared to women suggesting a greater sensitivity of the vasculature to high sodium in men.

Physiological responses to short-term exercise in the heat after creatine loading.

PURPOSE: This investigation was designed to examine the influence of creatine (Cr) supplementation on acute cardiovascular, renal, temperature, and fluid-regulatory hormonal responses to exercise for 35 min in the heat. METHODS: Twenty healthy men were matched and then randomly assigned to consume 0.3 g.kg(-1) Cr monohydrate (N = 10) or placebo (N = 10) for 7 d in a double-blind fashion. Before and after supplementation, both groups cycled for 30 min at 60-70% VO2(peak) immediately followed by three 10-s sprints in an environmental chamber at 37 degrees C and 80% relative humidity. RESULTS: Body mass was significantly increased (0.75 kg) in Cr subjects. Heart rate, blood pressure, and sweat rate responses to exercise were not significantly different between groups. There were no differences in rectal temperature responses in either group. Sodium, potassium, and creatinine excretion rates obtained from 24-h and exercise urine collection periods were not significantly altered in either group. Serum creatinine was elevated in the Cr group but within normal ranges. There were significant exercise-induced increases in cortisol, aldosterone, renin, angiotensin I and II, atrial peptide, and arginine vasopressin. The aldosterone response was slightly greater in the Cr (263%) compared with placebo (224%) group. Peak power was greater in the Cr group during all three 10-s sprints after supplementation and unchanged in the placebo group. There were no reports of adverse symptoms, including muscle cramping during supplementation or exercise. CONCLUSION: Cr supplementation augments repeated sprint cycle performance in the heat without altering thermoregulatory responses.

Quantification of mechanical and neural components of vagal baroreflex in humans.

Traditionally, arterial baroreflex control of vagal neural outflow is quantified by heart period responses to falling and/or rising arterial pressures (ms/mm Hg). However, it is arterial pressure-dependent stretch of barosensory vessels that determines afferent baroreceptor responses, which, in turn, generate appropriate efferent cardiac vagal outflow. Thus, mechanical transduction of pressure into barosensory vessel stretch and neural transduction of stretch into vagal outflow are key steps in baroreflex regulation that determine the conventional integrated input-output relation. We developed a novel technique for direct estimation of gain in both mechanical and neural components of integrated cardiac vagal baroreflex control. Concurrent, beat-by-beat measures of arterial pressures (Finapres), carotid diameters (B-mode ultrasonography), and R-R intervals (ECG lead II) were made during bolus vasoactive drug infusions (modified Oxford technique) in 16 healthy humans. The systolic carotid diameter/pressure relationship (r(2)=0.79+/-0.008, mean+/-SEM) provided a gain estimate of dynamic mechanical transduction of pressure into a baroreflex stimulus. The R-R interval/systolic diameter relationship (r(2)=0.77+/-0.009) provided a gain estimate of afferent-efferent neural transduction of baroreflex stimulus into a vagal response. Variance between repeated measures for both estimates was no different than that for standard gain (P>0.40). Moreover, in these subjects, the simple product of the 2 estimates almost equaled standard baroreflex gain (ms/mm Hg=0.98x+2.27; r(2)=0.93, P=0.001). This technique provides reliable information on key baroreflex components not distinguished by standard assessments and gives insight to dynamic mechanical and neural events during acute changes in arterial pressure.

Does reduced vascular stiffening fully explain preserved cardiovagal baroreflex function in older, physically active men?

BACKGROUND: We measured cardiovagal baroreflex gain and its vascular mechanical and neural components during dynamic baroreflex engagement in 10 young untrained men, 6 older untrained men, and 12 older, physically active men. METHODS AND RESULTS: Our newly developed assessment of beat-to-beat carotid diameters during baroreflex engagement estimates the mechanical transduction of pressure into barosensory stretch (diameter/pressure), the neural transduction of stretch into vagal outflow (R-R interval/diameter), and conventional integrated cardiovagal baroreflex gain (R-R interval/pressure). Integrated gain was lower in older untrained men than in young untrained men (6.8+/-1.2 versus 15.7+/-1.8 ms/mm Hg) due to both lower mechanical (9.1+/-1.0 versus 17.1+/-2.4 mm Hg/microm) and lower neural (0.57+/-0.10 versus 0.90+/-0.10 ms/microm) transduction. Integrated gain in older active men (13.3+/-2.7 ms/mm Hg) was comparable to that in young untrained men. This was achieved through mechanical transduction (12.1+/-1.4 mm Hg/microm) that was modestly higher than that in older untrained men and neural transduction (1.00+/-0.20 ms/microm) comparable to that in young untrained men. Across groups, both mechanical and neural components were related to integrated gain; however, the neural component carried greater predictive weight (beta=0.789 versus 0.588). CONCLUSIONS: Both vascular and neural deficits contribute to age-related declines in cardiovagal baroreflex gain; however, long-term physical activity attenuates this decline by maintaining neural vagal control.

Abnormal baroreflex responses in patients with idiopathic orthostatic intolerance.

BACKGROUND: Patients diagnosed with idiopathic orthostatic intolerance report symptoms of lightheadedness, fatigue, and nausea accompanied by an exaggerated tachycardia when assuming the upright posture. Often, these symptoms are present in the absence of any decrease in arterial pressure. We hypothesized that patients with idiopathic orthostatic intolerance would have impaired cardiac vagal and integrated baroreflex function, lower blood volume, and increased venous compliance. METHODS AND RESULTS: Sixteen patients and 14 healthy control subjects underwent the modified Oxford technique to assess cardiac vagal baroreflex sensitivity. Progressive lower-body negative pressure (to -50 mm Hg; LBNP) was used to examine the integrated baroreflex response to progressive hypovolemic stimuli. Blood volume and venous compliance were also assessed. Patients with idiopathic orthostatic intolerance had lower cardiac vagal baroreflex sensitivity (12+/-1 versus 25+/-4 ms/mm Hg; P

Age and renal prostaglandin inhibition during exercise and heat stress.

Aging is associated with a number of physiological changes that may cause the kidney to rely to a greater extent on vasodilatory PGs for normal functioning. Acute exercise has been shown to cause renal vasoconstriction that may be partially buffered by vasodilatory PGs. To determine the relative importance of renal PGs during exercise in older adults, we compared the renal effects of the PG inhibitor ibuprofen (1.2 g/day for 3 days) vs. a placebo control in a cohort of eight younger (24 +/- 2 yr) and eight older (64 +/- 2 yr) women during treadmill exercise ( approximately 57% maximal oxygen consumption) in the heat (36 degrees C). This over-the-counter dose of ibuprofen reduced renal PG (i.e., PGE2) excretion by 47% (P < 0. 05). Acute exercise in the heat caused dramatic decreases in glomerular filtration rate, renal blood flow, and sodium excretion in both age groups. PG inhibition was associated with greater decreases in urine production and free water clearance (P < 0.05). There were no drug-related declines in glomerular filtration rate or renal blood flow. We conclude that PG inhibition has only modest effects on renal function during exercise. Also, the lack of hemodynamic changes with PG inhibition indicates that healthy well-hydrated older women are not in a renal PG-dependent state.

Effects of acetaminophen and ibuprofen on renal function in the stressed kidney.

Exercise, salt restriction, and/or dehydration causes transient reductions in renal function that may be buffered by vasodilatory prostaglandins (PGs). Over-the-counter (OTC) analgesics have the potential to alter renal hemodynamics by inhibiting renal PGs. Therefore, we tested the renal effects of the maximal recommended dose of acetaminophen (Acet, 4 g/day) and ibuprofen (Ibu, 1.2 g/day) vs. a placebo (Pl) in humans subjected to progressive renal stresses. After baseline measurements, 12 fit young (25 +/- 1 yr) men and women underwent 3 days of a low (10 meq/day)-sodium diet while taking one of the drugs or Pl (crossover design). Day 4 involved dehydration (-1.6% body wt) followed by 45 min of treadmill exercise (65% maximal O2 uptake) in the heat (36 degreesC). These combined stressors caused dramatic decreases in effective renal plasma flow, glomerular filtration rate (GFR), and sodium excretion. Baseline GFR (range: 118-123 ml/min) decreased to 78 +/- 4, 73 +/- 5, and 82 +/- 5 ml/min postexercise in the Acet, Ibu, and Pl trials, respectively, with a significantly greater decrease in GFR in the Ibu trial (P < 0. 05 vs. Pl). OTC Ibu has small but statistically significant effects on GFR during exercise in a sodium- and volume-depleted state; OTC Acet was associated with no such effects.

Decreased active vasodilator sensitivity in aged skin.

Older men and women respond to local and reflex-mediated heat stress with an attenuated increase in cutaneous vascular conductance (CVC). This study was performed to test the hypothesis that an augmented or sustained noradrenergic vasoconstriction (VC) may play a role in this age-related difference. Fifteen young (22 +/- 1 yr) and 15 older (66 +/- 1 yr) men exercised at 50% peak oxygen uptake in a 36 degrees C environment. Skin perfusion was monitored at two sites on the right forearm by laser-Doppler flowmetry: one site pretreated with bretylium tosylate (BT) to block the local release of norepinephrine and thus VC and an adjacent control site. Blockade of reflex VC was verified during whole body cooling using a water-perfused suit. CVC (perfusion divided by mean arterial pressure) at each site was reported as a percentage of the maximal CVC (%CVCmax) induced at the end of each experiment by prolonged local heating at 42 degrees C. Neither age nor BT affected the %CVCmax (75-86%) attained at high core temperatures. During the early rise phase of CVC, the %CVCmax-change in esophageal temperature (delta T(es)) curve was shifted to the right in the older men (effective delta T(es) associated with 50% CVC response for young, 0.22 +/- 0.04 and 0.39 +/- 0.04 degrees C and for older, 0.73 +/- 0.04 and 0.85 +/- 0.04 degrees C at control and BT sites, respectively). BT had no interactive effect on this age difference, suggesting a lack of involvement of the VC system in the attenuated CVC response of individuals over the age of 60 yr. Additionally, increases in skin vascular conductance were quantitatively compared by measuring increases in total forearm vascular conductance (FVC, restricted to the forearm skin under these conditions). After the initial approximately 0.2 degrees C increase in T(es), FVC was 40-50% lower in the older men (P < 0.01) for the remainder of the exercise. Decreased active vasodilator sensitivity to increasing core temperature, coupled with structural limitations to vasodilation, appears to limit the cutaneous vascular response to exertional heat stress in older subjects.