https://www.thelancet.com/pdfs/journals/lancet/PIIS0140673699073304.pdf

Risks of untreated and treated isolated systolic hypertension in the elderly: meta-analysis of outcome trials

The overall scheme for control is as follows: central command sets basic patterns of cardiovascular effector activity, which is modulated via muscle chemo- and mechanoreflexes and arterial mechanoreflexes (baroreflexes) as appropriate error signals develop. A key question is whether the primary error corrected is a mismatch between blood flow and metabolism (a flow error that accumulates muscle metabolites that activate group III and IV chemosensitive muscle afferents) or a mismatch between cardiac output (CO) and vascular conductance [a blood pressure (BP) error] that activates the arterial baroreflex and raises BP. Reduction in muscle blood flow to a threshold for the muscle chemoreflex raises muscle metabolite concentration and reflexly raises BP by activating chemosensitive muscle afferents. In isometric exercise, sympathetic nervous activity (SNA) is increased mainly by muscle chemoreflex whereas central command raises heart rate (HR) and CO by vagal withdrawal. Cardiovascular control changes for dynamic exercise with large muscles. At exercise onset, central command increases HR by vagal withdrawal and "resets" the baroreflex to a higher BP. As long as vagal withdrawal can raise HR and CO rapidly so that BP rises quickly to its higher operating point, there is no mismatch between CO and vascular conductance (no BP error) and SNA does not increase. Increased SNA occurs at whatever HR (depending on species) exceeds the range of vagal withdrawal; the additional sympathetically mediated rise in CO needed to raise BP to its new operating point is slower and leads to a BP error. Sympathetic vasoconstriction is needed to complete the rise in BP. The baroreflex is essential for BP elevation at onset of exercise and for BP stabilization during mild exercise (subthreshold for chemoreflex), and it can oppose or magnify the chemoreflex when it is activated at higher work rates. Ultimately, when vascular conductance exceeds cardiac pumping capacity in the most severe exercise both chemoreflex and baroreflex must maintain BP by vasoconstricting active muscle.

Reflex control of the circulation during exercise: chemoreflexes and mechanoreflexes

Purpose: A meta-analysis of randomized trials studying the effect of nonsteroidal anti-inflammatory drugs (NSAIDs) on blood pressure. Data Sources and Study Selection: Eight databases were searched...

Do Nonsteroidal Anti-inflammatory Drugs Affect Blood Pressure? A Meta-Analysis

Muscular exercise requires transitions to and from metabolic rates often exceeding an order of magnitude above resting and places prodigious demands on the oxidative machinery and O2-transport pathway. The science of kinetics seeks to characterize the dynamic profiles of the respiratory, cardiovascular, and muscular systems and their integration to resolve the essential control mechanisms of muscle energetics and oxidative function: a goal not feasible using the steady-state response. Essential features of the O2 uptake (VO2) kinetics response are highly conserved across the animal kingdom. For a given metabolic demand, fast VO2 kinetics mandates a smaller O2 deficit, less substrate-level phosphorylation and high exercise tolerance. By the same token, slow VO2 kinetics incurs a high O2 deficit, presents a greater challenge to homeostasis and presages poor exercise tolerance. Compelling evidence supports that, in healthy individuals walking, running, or cycling upright, VO2 kinetics control resides within the exercising muscle(s) and is therefore not dependent upon, or limited by, upstream O2-transport systems. However, disease, aging, and other imposed constraints may redistribute VO2 kinetics control more proximally within the O2-transport system. Greater understanding of VO2 kinetics control and, in particular, its relation to the plasticity of the O2-transport/utilization system is considered important for improving the human condition, not just in athletic populations, but crucially for patients suffering from pathologically slowed VO2 kinetics as well as the burgeoning elderly population.

Oxygen Uptake Kinetics

Determination of an 'anaerobic threshold' plays an important role in the appreciation of an incremental cardiopulmonary exercise test and describes prominent changes of blood lactate accumulation with increasing workload. Two lactate thresholds are discerned during cardiopulmonary exercise testing and used for physical fitness estimation or training prescription. A multitude of different terms are, however, found in the literature describing the two thresholds. Furthermore, the term 'anaerobic threshold' is synonymously used for both, the 'first' and the 'second' lactate threshold, bearing a great potential of confusion. The aim of this review is therefore to order terms, present threshold concepts, and describe methods for lactate threshold determination using a three-phase model with reference to the historical and physiological background to facilitate the practical application of the term 'anaerobic threshold'.

Methodological approach to the first and second lactate threshold in incremental cardiopulmonary exercise testing.

The ventilatory (anaerobic) threshold for short-term exercise was defined as the work rate or O2 uptake (VO2) immediately below the work rate at which ventilation increased disproportionately relative to work rate or VO2, and the ventilatory threshold for long-term exercise as the work rate or VO2 immediately below the work rate at which ventilation continued to increase with time rather than attain a steady state. The purpose of the present study was to investigate how both thresholds relate to each other and how they relate to other measures of physical performance capacity. The subjects were eight healthy males, 20-53 yr of age. Maximal performance capacity was estimated by measurements of maximal O2 uptake (VO2 max) and by endurance performance during a 12-min distance run. A high interrelationship was found between the two thresholds (r = 0.84), and each threshold expressed in VO2 (ml X min-1 X kg-1) correlated highly with VO2 max (r = 0.87 and r = 0.75, for short-term and long-term exercise, respectively). When the two thresholds were expressed as a percentage of VO2 max, neither threshold showed a significant relationship with VO2 max. Endurance performance was significantly correlated with both the ventilatory threshold for short-term and long-term exercise (r = 0.73 and 0.82, respectively). A stepwise multiple regression analysis indicated that the distance run in 12 min was best predicted by VO2 max (R2 = 0.66) or the ventilatory threshold for long-term exercise (R2 = 0.63). It is concluded that the ventilatory threshold for long-term exercise is a more specific measure to explain running performance than is the threshold during graded exercise.

Ventilatory thresholds during short- and long-term exercise

This double-blind placebo-controlled study investigated whether indomethacin-induced (500 mg/3 days) prostaglandin synthesis inhibition (PG inhibition) affected systemic hemodynamics and several humoral factors in nine sodium-replete normal humans, during exercise. Independent of the level of physical activity, PG inhibition was accompanied by small but significant (P less than 0.001) increases in systolic (+4.3 mmHg) and diastolic (+1.8 mmHg) intra-arterial pressure: the changes in cardiac output (determined noninvasively), systemic vascular resistance, and exercise capacity did not reach a level of statistical significance. After PG inhibition, plasma 13,14-dihydro-15-keto/prostaglandin F2 alpha, plasma renin, and aldosterone were reduced (P less than 0.001) at rest sitting and exercise, but PG inhibition did not prevent the exercise-induced stimulation of the plasma renin-aldosterone system. The urinary sodium excretion, averaging 156 meq/24 h during placebo, decreased (P less than 0.001) by 28 meq/24 h during PG inhibition: urinary aldosterone and kallikrein and the plasma catecholamines remained unchanged. In resting and exercising sodium-replete subjects, prostaglandins seem to exert a depressor effect on the systemic circulation and to increase plasma renin activity, but they are probably not involved in the exercise-related stimulation of the plasma renin-aldosterone system.

Hemodynamic and humoral effects of prostaglandin inhibition in exercising humans.

1. The systemic circulation at rest and during exercise was studied in ten normal male volunteers, after placebo on one occasion and after acute intravenous administration of the serotonergic antagonist ketanserin on another occasion. The effects of ketanserin on the components of the renin—angiotensin—aldosterone system, on plasma catecholamines and on exercise capacity for graded uninterrupted exercise were also investigated. 2. At rest in recumbency rapid intravenous injection of 10 mg of ketanserin, followed by a continuous infusion of 2 mg/h, produced an acute but transient fall in mean intra-arterial pressure of 6 mmHg compared with placebo. After 15 min the mean arterial pressure with ketanserin was within 2 mmHg of the mean pressure with placebo. In the sitting position both at rest and up to 30% of maximal work rate, the mean arterial pressure during ketanserin did not differ from the pressure on placebo. However, at higher levels of physical activity the rise in mean arterial pressure was lower with ketanserin; the pressure achieved with placebo was 7.5 mmHg higher at maximal work rate. Heart rate and cardiac output were significantly higher during ketanserin. 3. When the subjects were lying down and resting, plasma noradrenaline and adrenaline levels, plasma renin activity and angiotensin II concentration were not affected by ketanserin; however, these values were higher in the sitting position both at rest and during exercise. Plasma aldosterone was reduced by ketanserin during exercise and also when the subject was resting in the recumbent position. 4. Exercise capacity as measured by peak oxygen uptake was similar during ketanserin (3.09 ± se 0.12 litres/min) and during placebo (3.11 ± 0.13). 5. The data suggest that 5-hydroxytryptamine can have only a small role, if any, in pressure homoeostasis in sodium replete man at rest in recumbency. At moderate and heavy levels of exercise, the results are compatible with a role for 5-hydroxytryptamine in pressure regulation. Activation of the sympathetic nervous system by ketanserin is suggested by increases of plasma catecholamines, heart rate, cardiac output and plasma renin. The suppression of plasma aldosterone suggests that 5-hydroxytryptamine may have a role in the regulation of aldosterone secretion which is independent of angiotensin II.

Responses of the systemic circulation and of the renin-angiotensin-aldosterone system to ketanserin at rest and exercise in normal man.

Treatment of 8 hypertensive elderly subjects with atenolol or with labetalol did not affect exercise performance, except after the development of circulatory congestion in 1 patient. Treatment with beta blockers did not alter the response to an exercise training programme in 15 elderly patients with ischaemic heart disease, as compared with 11 patients without such treatment.

A Cattaert

Papers

Ventilatory thresholds during short- and long-term exercise

Hemodynamic and humoral effects of prostaglandin inhibition in exercising humans.

Responses of the systemic circulation and of the renin-angiotensin-aldosterone system to ketanserin at rest and exercise in normal man.

The effects of beta blockers on exercise capacity and on training response in elderly subjects.

Epidemiology of treated, compared to untreated, hypertension