Omega-3 polyunsaturated fatty acid supplementation reduces blood pressure but not renal vasoconstrictor response to orthostatic stress in healthy older adults.

Older adults exhibit augmented renal vasoconstriction during orthostatic stress compared to young adults. Consumption of omega-3 polyunsaturated fatty acids, such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) found in fish oil (FO), modulates autonomic nerve activity. However, the effect of omega-3 polyunsaturated fatty acid consumption on the renal vasoconstrictor response to orthostatic stress in young and older adults is unknown.

Omega-3 polyunsaturated fatty acid supplementation attenuates blood pressure increase at onset of isometric handgrip exercise in healthy young and older humans.

Aging is associated with alterations of autonomic nerve activity, and dietary intake of omega-3 polyunsaturated fatty acids, such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) found in fish oil (FO), can modulate autonomic nerve activity. However, the effect of omega-3 polyunsaturated fatty acid consumption on age-related cardiovascular responses at the onset of isometric handgrip exercise, a time of rapid autonomic adjustments, is unknown. Accordingly, 14 young (25 ± 1 years; mean ± SE) and 15 older (64 ± 2 years) healthy subjects ingested 4 g FO daily for 12 weeks.

Aging augments renal vasoconstrictor response to orthostatic stress in humans.

The ability of the human body to maintain arterial blood pressure (BP) during orthostatic stress is determined by several reflex neural mechanisms. Renal vasoconstriction progressively increases during graded elevations in lower body negative pressure (LBNP). This sympathetically mediated response redistributes blood flow to the systemic circulation to maintain BP.

Effect of omega-3 polyunsaturated fatty acid supplementation on central arterial stiffness and arterial wave reflections in young and older healthy adults.

Increased central arterial stiffness and enhanced arterial wave reflections may contribute to increased risk of cardiovascular disease development with advancing age. Omega-3 polyunsaturated fatty acid (n-3) ingestion may reduce cardiovascular risk via favorable effects exerted on arterial structure and function. We determined the effects of n-3 supplementation (4 g/day for 12 weeks) on important measures of central arterial stiffness (carotid-femoral pulse wave velocity; PWV) and arterial wave reflection (central augmentation index) in young (n = 12; 25 ± 1-year-old, mean ± SE) and older (n = 12; 66 ± 2) healthy adults.

Using thermal stress to model aspects of disease states.

Exposure to acute heat or cold stress elicits numerous physiological responses aimed at maintaining body temperatures. Interestingly, many of the physiological responses, mediated by the cardiovascular and autonomic nervous systems, resemble aspects of, or responses to, certain disease states. The purpose of this Perspective is to highlight some of these areas in order to explore how they may help us better understand the pathophysiology underlying aspects of certain disease states.

Ventilatory responses to chemoreflex stimulation are not enhanced by angiotensin II in healthy humans.

The chemoreflexes exert significant control over respiration and sympathetic outflow. Abnormalities in chemoreflex function may contribute to various disease processes. Based on prior animal studies, we developed the hypothesis that acutely elevating circulating angiotensin II levels into the pathophysiological range increases chemoreflex responsiveness in healthy humans.

Neurogenic and sympathoexcitatory actions of NaCl in hypertension.

Excess dietary salt intake is a major contributing factor to the pathogenesis of salt-sensitive hypertension. Strong evidence suggests that salt-sensitive hypertension is attributed to renal dysfunction, vascular abnormalities, and activation of the sympathetic nervous system. Indeed, sympathetic nerve transections or interruption of neurotransmission in various brain centers lowers arterial blood pressure (ABP) in many salt-sensitive models.

Contribution of sympathetic activation to coronary vasodilatation during the cold pressor test in healthy men: effect of ageing.

The sympathetic nervous system is an important regulator of coronary blood flow. The cold pressor test (CPT) is a powerful sympathoexcitatory stressor. We tested the hypotheses that: (1) CPT-induced sympathetic activation elicits coronary vasodilatation in young adults that is impaired with advancing age and (2) combined α- and β-adrenergic blockade diminishes/abolishes these age-related differences.

Effect of cocoa/chocolate ingestion on brachial artery flow-mediated dilation and its relevance to cardiovascular health and disease in humans.

Prospective studies indicate that high intake of dietary flavanols, such as those contained in cocoa/chocolate, are associated with reduced rates of cardiovascular-related morbidity and mortality in humans. Numerous mechanisms may underlie these associations such as favorable effects of flavanols on blood pressure, platelet aggregation, thrombosis, inflammation, and the vascular endothelium. The brachial artery flow-mediated dilation (FMD) technique has emerged as a robust method to quantify endothelial function in humans.

Altered coronary vascular control during cold stress in healthy older adults.

Cardiovascular-related mortality increases in the cold winter months, particularly in older adults. Previously, we reported that determinants of myocardial O(2) demand, such as the rate-pressure product, increase more in older adults compared with young adults during cold stress. The aim of the present study was to determine if aging influences the coronary hemodynamic response to cold stress in humans.

Dose-dependent increases in flow-mediated dilation following acute cocoa ingestion in healthy older adults.

An inverse relation exists between intake of flavonoid-rich foods, such as cocoa, and cardiovascular-related mortality. Favorable effects of flavonoids on the endothelium may underlie these associations. We performed a randomized, double-blind, placebo-controlled study to test the hypothesis that acute cocoa ingestion dose dependently increases endothelium-dependent vasodilation, as measured by an increase in brachial artery flow-mediated dilation (FMD), in healthy older adults.

Adrenergic mechanisms do not contribute to age-related decreases in calf venous compliance.

Limb venous compliance decreases with advancing age, even in healthy humans. To test the hypothesis that adrenergic mechanisms contribute to age-associated reductions in limb venous compliance, we measured calf venous compliance before and during acute systemic α- and β-adrenergic blockade in eight young (27 ± 1 yr old, mean ± SE) and eight older healthy men (67 ± 2 yr old). Calf venous compliance was determined in supine subjects by inflating a thigh-collecting cuff to 60 mmHg for 8 min and then decreasing it (1 mmHg/s) to 0 mmHg while calf volume was indexed with a strain gauge.

Effect of aging on cardiac function during cold stress in humans.

To determine whether skin surface cooling increases left ventricular preload and contractility to a greater extent in older compared with young adults we studied 11 young (28 +/- 2 yr; means +/- SE) and 11 older (64 +/- 3 yr) adults during normothermia (35 degrees C water perfused through a tube-lined suit) and cooling (15 degrees C water perfused for 20 min) using standard and tissue Doppler echocardiography. Cooling significantly decreased skin surface temperature in young (Delta2.8 +/- 0.

Aging affects the cardiovascular responses to cold stress in humans.

Cardiovascular-related mortality peaks during cold winter months, particularly in older adults. Acute physiological responses, such as increases in blood pressure, in response to cold exposure may contribute to these associations. To determine whether the blood pressure-raising effect (pressor response) of non-internal body temperature-reducing cold stress is greater with age, we measured physiological responses to 20 min of superficial skin cooling, via water-perfused suit, in 12 younger [25 +/- 1 (SE) yr old] and 12 older (65 +/- 2 yr old) adults.

High-dose ascorbic acid infusion abolishes chronic vasoconstriction and restores resting leg blood flow in healthy older men.

Resting whole leg blood flow and vascular conductance decrease linearly with advancing age in healthy adult men. The potential role of age-related increases in oxidative stress in these changes is unknown. Resting leg blood flow during saline and ascorbic acid infusion was studied in 10 young (25 +/- 1 yr) and 11 older (63 +/- 2 yr) healthy normotensive men.

Skin-surface cooling elicits peripheral and visceral vasoconstriction in humans.

Skin-surface cooling elicits a pronounced systemic pressor response, which has previously been reported to be associated with peripheral vasoconstriction and may not fully account for the decrease in systemic vascular conductance. To test the hypothesis that whole body skin-surface cooling would also induce renal and splanchnic vasoconstriction, 14 supine subjects performed 26 skin-surface cooling trials (15-18 degrees C water perfused through a tube-lined suit for 20 min). Oral and mean skin temperature, heart rate, stroke volume (Doppler ultrasound), mean arterial blood pressure (MAP), cutaneous blood velocity (laser-Doppler), and mean blood velocity of the brachial, celiac, renal, and superior mesenteric arteries (Doppler ultrasound) were measured during normothermia and skin-surface cooling.

Effect of baroreflex loading on the responsiveness of the vestibulosympathetic reflex in humans.

Activation of the vestibular otolith organs with head-down rotation (HDR) increases muscle sympathetic nerve activity (MSNA) in humans. Previously, we demonstrated this vestibulosympathetic reflex (VSR) elicits increases in MSNA during baroreflex unloading (i.e.

Effect of acute hyperlipidemia on autonomic and cardiovascular control in humans.

Blood lipids may detrimentally affect autonomic and circulatory control. We tested the hypotheses that acute elevations in free fatty acids and triglycerides (acute hyperlipidemia) impair baroreflex control of cardiac period [cardiovagal baroreflex sensitivity (BRS)] and muscle sympathetic nerve activity (MSNA: sympathetic BRS), increase MSNA at rest, and augment physiological responses to exercise. Eighteen young adults were examined in this randomized, double-blinded, and placebo-controlled study.

Effect of aging on baroreflex function in humans.

Arterial blood pressure (BP) is regulated via the interaction of various local, humoral, and neural factors. In humans, the major neural pathway for acute BP regulation involves the baroreflexes. In response to baroreceptor activation/deactivation, as occurs during transient changes in BP, key determinants of BP, such as cardiac period/heart rate (via the sympathetic and parasympathetic nervous system) and vascular resistance (via the sympathetic nervous system), are modified to maintain BP homeostasis.

Impaired flow-mediated dilation with age is not explained by L-arginine bioavailability or endothelial asymmetric dimethylarginine protein expression.

Aging is associated with a decline in vascular endothelial function, manifesting in part as impaired flow-mediated arterial dilation (FMD), but the underlying mechanisms are uncertain. Impaired FMD may be mediated in part by a decrease in synthesis of nitric oxide by endothelial nitric oxide synthase, and in clinical populations this has been attributed to competitive inhibition of l-arginine binding sites by asymmetric dimethylarginine (ADMA). If this mechanism is involved in the age-associated decline in FMD, increasing l-arginine concentration may swing the competitive balance in favor of l-arginine binding, restoring nitric oxide synthesis, and enhancing FMD in older humans.