Prevailing Blood Pressure Research Articles

Pressure Building Against the Clock: The Impact of Circadian Misalignment on Blood Pressure.

Misalignment between the endogenous biological timing system and behavioral activities (i.e., sleep/wake, eating, activity) contributes to adverse cardiovascular health. In this review, we discuss the effects of recurring circadian misalignment on blood pressure regulation and the implications for hypertension development. Additionally, we highlight emerging therapeutic approaches designed to mitigate the negative cardiovascular consequences elicited by circadian disruption. Circadian misalignment elicited by work schedules that require individuals to be awake during the biological night (i.e., shift work) alters 24-h blood pressure rhythms. Mechanistically, circadian misalignment appears to alter blood pressure via changes in autonomic nervous system balance, variations to sodium retention, dysregulation of endothelial vasodilatory responsiveness, and activation of proinflammatory mechanisms. Recurring circadian misalignment produced by a mismatch in sleep timing on free days vs. work days (i.e., social jetlag) appears to have no direct effects on prevailing blood pressure levels in healthy adults; though, circadian disruptions resulting from social jetlag may increase the risk of hypertension through enhanced sympathetic activation and/or obesity. Furthermore, social jetlag assessment may be a useful metric in shift work populations where the magnitude of circadian misalignment may be greater than in the general population. Circadian misalignment promotes unfavorable changes to 24-h blood pressure rhythms, most notably in shift working populations. While light therapy, melatonin supplementation, and the timing of drug administration may improve cardiovascular outcomes, interventions designed to target the effects of circadian misalignment on blood pressure regulation are warranted.

Muscle Metaboreflex Modulation of Spontaneous Cardiac Baroreflex Sensitivity: Does Sex Matter?

It is well established that during exercise, the arterial baroreflex is reset to operate around the prevailing blood pressure in an exercise intensity‐dependent manner. This exercise‐induced modulation of baroreflex function is mediated by central signals and by afferent signals arising from working skeletal muscle that are composed of mechanically and metabolically sensitive afferents. Previous studies in humans examining the influence of metabolically sensitive skeletal muscle afferents (i.e., muscle metaboreflex) on cardiac baroreflex sensitivity (cBRS) have found equivocal results reporting increases, decreases, or no change in sensitivity. The reason behind these discrepancies could be attributable to variation in the methods used to assess baroreflex function, exercise modality and intensity, size of exercising muscle mass, and, less discussed, but also relevant, the inclusion of both men and women. This becomes important given a plethora of studies indicating that sex plays a pivotal role when it comes to blood pressure regulation. Given this, the aim of the present study was to investigate the effect of isolated muscle metaboreflex activation on cBRS and the potential sex‐related differences in this interaction. Forty healthy and physically active volunteers (20 men), aged 18–30 years were recruited. All women were non‐oral contraceptives users and performed experiments in the early follicular phase of the menstrual cycle. After 10 minutes rest period, the subjects performed 90s of isometric handgrip (IHG) at 40% of maximal voluntary contraction followed by 3‐min of post exercise ischemia (PEI) to isolate the muscle metaboreflex. Beat‐to‐beat heart rate (HR ‐ electrocardiography) and arterial blood pressure (finger photopletysmography) were continuously measured. Spontaneous cBRS was assessed for all combined sequences (Gainall), and also separately upward (Gainup) and downward (Gaindown) using the sequence technique. HR variability was measured in time (RMSSD ‐ standard deviation of the RR intervals) and frequency domains (LF – low and HF – high frequency power). Resting MBP was lower in women than men (P < 0.01). MBP increased from rest during IHG and remained elevated during PEI in both men and women. However, the magnitude of these responses was greater in men. Resting cBRS was similar between men and women. During PEI, men exhibited an increase in cBRS (Gainall: Δ3.0 ± 1.1 ms mmHg‐1, P = 0.03; Gainup: Δ4.4 ± 2.1 ms mmHg‐1, P = 0.04; and Gaindown: Δ3.3 ± 1.4 ms mmHg‐1, P = 0.03). In contrast, cBRS was unchanged during PEI in women (Gainall: Δ0.6 ± 0.7 ms mmHg‐1, P = 0.10; Gainup: Δ0.3 ± 0.7 ms mmHg‐1, P = 0.27; and Gaindown: Δ0.2 ± 1.1 ms mmHg‐1, P = 0.43). At rest, HF and LF power were lower in women compared with men, whereas RMSSD and LF/HF ratio were similar. During PEI, men exhibited a highest increase in RMSSD and HF compared to women, while LF power was unchanged in both groups. In addition, LF/HF ratio decreased in men and was unchanged in women. These findings indicate that the muscle metaboreflex activation modulates spontaneous cBRS in a sex dependent manner.Support or Funding InformationBrazilian National Council of Scientific and Technological Development (CNPq); Foundation for Research Support of Federal District (FAPDF); Brazilian Federal Agency for Support and Evaluation of Graduate Education (CAPES).This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Left ventricular function and contractile reserve in patients with hypertension.

An impaired contractile reserve (CR) may be an early manifestation of left ventricular (LV) systolic dysfunction in hypertensive patients. Using normotensive patients as controls, we examined LV CR and its correlates in hypertensive patients. One hundred and twenty-nine (68 men, aged 58.6 ± 9.5 years, 73 had hypertension) patients underwent dobutamine echocardiography. Patients with significant coronary or valvular disease, previous myocardial infarction or revascularization, and diabetes were excluded. LV ejection fraction (LVEF), global longitudinal strain (GLS), circumferential, and radial strain were measured at rest and at low-dose dobutamine. Absolute CR was calculated as the difference in LVEF and multi-directional strain between low-dose dobutamine and their corresponding resting values. Relative CR is the ratio of absolute CR to their corresponding resting values. Hypertensive patients, compared with controls, have significantly impaired GLS at rest (-16.8 ± 2.2% vs. -19.6 ± 1.5%, P < 0.0001) and at low-dose dobutamine (-17.9 ± 2.7% vs. -22.8 ± 2.6%, P < 0.0001). Absolute and relative GLS CR were significantly lower in hypertensive patients (-1.1 ± 2.1% vs. -3.2 ± 2.2% and 7.4 ± 13.9% vs. 16.4 ± 11.7%, respectively, both P < 0.001). Circumferential strain was preserved at rest but impaired at low-dose dobutamine in hypertensive patients (-23.0 ± 4.1% vs. -25.2 ± 3.4%, P = 0.002). There were no differences in LVEF or radial strain between the groups. LV wall thickness and systolic blood pressure correlated significantly with GLS at rest and at low-dose dobutamine. LV wall thickness is the only independent correlates of absolute CR. Compared with controls, hypertensive patients have impaired LV GLS at rest and impaired CR despite normal LVEF. Impaired CR correlated with LV wall thickness but independent of prevailing blood pressure.

Hypertensive Patients Have Impaired Left Ventricular Contractile Reserve Despite Normal Ejection Fraction

Hypertension (HT) may lead to LV systolic impairment through chronic pressure overload. LV hypertrophy and systolic dysfunction occur late. An impaired contractile reserve (CR) may be an early manifestation of LV dysfunction in hypertensive patients. We examined CR and its correlates in hypertensive patients and compared that with normotensive controls. Methods: 129 prospectively recruited patients (68 men, aged 58.6 ± 9.5 years) underwent dobutamine echocardiography. Patients with diabetes, coronary disease, or significant valvular disease were excluded. 72 patients (56%) had treated HT. LV global longitudinal strain (GLS) was measured at rest and at low dose dobutamine. Absolute CR was calculated as the difference in GLS between low dose and resting values. Relative CR is the ratio of absolute CR to resting GLS. Results: There was no difference in LV ejection fraction between hypertensive patients and controls (64.5 ± 6.1% vs 64.5 ± 6.6% at rest, 72.1 ± 6.6% vs 71.2 ± 6.9% at low dose dobutamine; both p = NS). LVGLS in hypertensive patients was significantly impaired at rest (-16.8 ± 2.2% vs -19.5 ± 1.5%; both p < 0.001) and at low dose dobutamine (-17.9 ± 2.7% vs -22.7 ± 2.6%; both p < 0.001). More importantly, both the absolute and relative CR were significantly lower in hypertensive patients (-1.12% vs -3.17%; 7.24% vs 16.4% respectively, both p < 0.001). CR was not correlated with LV mass, prevailing blood pressure, septal e’ velocities, E/e’ ratio. Conclusions: Compared with controls, hypertensive patients not only had impaired LV GLS at rest, but also an impaired ability to augment contractility with inotropic stimulation, i.e. CR. This impaired CR is independent of LV mass, diastolic function or filling pressures.

Altered Cardiovascular Rhythmicity in Children Born Small for Gestational Age

Low birth weight is frequently associated with a disproportionately high incidence of cardiovascular disease, diabetes mellitus, and kidney disease in adulthood. Epidemiological studies have identified an inverse association between low birth weight or being small for gestational age and hypertension in adulthood. We hypothesized that children born with low birth weight might have altered circadian and ultradian cardiovascular rhythmicity independent of the prevailing blood pressure level. Twenty-four-hour ambulatory blood pressure and heart rate rhythmicity was prospectively evaluated by Fourier analysis in a cohort of healthy children born with low birth weight and compared with normative pediatric data. Seventy-five children born small for gestational age (mean age, 8.1±2.2 years) and 139 controls matched for age and sex were investigated. In addition to increased 24-hour, daytime, and especially nighttime blood pressure levels (P<0.05), children born small for gestational age exhibited blunted circadian (24-hour) and ultradian (12-, 8-, and 6-hour) blood pressure rhythmicity (P<0.05). In a multivariate analysis including children born with low birth weight and controls, being born with low birth weight independently influenced ultradian blood pressure rhythmicity, whereas in a multivariate analysis including children born with low birth weight only, circadian and ultradian rhythms were independently influenced by catch-up growth, gestational age, and blood pressure level. This study demonstrates blunted circadian and ultradian cardiovascular rhythmicity in prepubertal children born small for gestational age, independent from the presence of arterial hypertension. Circadian and ultradian rhythms may be sensitive indicators for detecting subtle early abnormalities of cardiovascular regulation.

Pulse Wave Velocity as Marker of Preclinical Arterial Disease: Reference Levels in a Uruguayan Population Considering Wave Detection Algorithms, Path Lengths, Aging, and Blood Pressure

Carotid-femoral pulse wave velocity (PWV) has emerged as the gold standard for non-invasive evaluation of aortic stiffness; absence of standardized methodologies of study and lack of normal and reference values have limited a wider clinical implementation. This work was carried out in a Uruguayan (South American) population in order to characterize normal, reference, and threshold levels of PWV considering normal age-related changes in PWV and the prevailing blood pressure level during the study. A conservative approach was used, and we excluded symptomatic subjects; subjects with history of cardiovascular (CV) disease, diabetes mellitus or renal failure; subjects with traditional CV risk factors (other than age and gender); asymptomatic subjects with atherosclerotic plaques in carotid arteries; patients taking anti-hypertensives or lipid-lowering medications. The included subjects (n = 429) were categorized according to the age decade and the blood pressure levels (at study time). All subjects represented the “reference population”; the group of subjects with optimal/normal blood pressures levels at study time represented the “normal population.” Results. Normal and reference PWV levels were obtained. Differences in PWV levels and aging-associated changes were obtained. The obtained data could be used to define vascular aging and abnormal or disease-related arterial changes.

Are the Arms and Legs in Competition for Cardiac Output?

Oxygen transport to working skeletal muscles is challenged during whole-body exercise. In general, arm-cranking exercise elicits a maximal oxygen uptake (VO2max) corresponding to approximately 70% of the value reached during leg exercise. However, in arm-trained subjects such as rowers, cross-country skiers, and swimmers, the arm VO2max approaches or surpasses the leg value. Despite this similarity between arm and leg VO2max, when arm exercise is added to leg exercise, VO2max is not markedly elevated, which suggests a central or cardiac limitation. In fact, when intense arm exercise is added to leg exercise, leg blood flow at a given work rate is approximately 10% less than during leg exercise alone. Similarly, when intense leg exercise is added to arm exercise, arm blood flow and muscle oxygenation are reduced by approximately 10%. Such reductions in regional blood flow are mainly attributed to peripheral vasoconstriction induced by the arterial baroreflex to support the prevailing blood pressure. This putative mechanism is also demonstrated when the ability to increase cardiac output is compromised; during exercise, the prevailing blood pressure is established primarily by an increase in cardiac output, but if the contribution of the cardiac output is not sufficient to maintain the preset blood pressure, the arterial baroreflex increases peripheral resistance by augmenting sympathetic activity and restricting blood flow to working skeletal muscles.

Clinical value of ambulatory blood pressure monitoring in the assessment of antihypertensive therapy

Non-invasive ambulatory blood pressure monitoring (ABPM) is particularly useful for assessing the efficacy of antihypertensive drugs. It provides a large number of blood pressure readings during daytime as well as night-time, which results in a more precise assessment of prevailing blood pressure than can be obtained from sporadic measurements taken by a doctor. Because of this greater precision ABPM reduces the number of patients required in clinical trials to demonstrate differences. It also allows one to define precisely the profile of the blood-pressure-lowering effect of a given drug. Placebo has little effect on ABPM. Thus, a placebo phase is not absolutely necessary. ABPM makes it possible to evaluate the efficacy of an antihypertensive medication by analysing data for patients with a placebo effect separately from data for true responders to the medication. In everyday practice ABPM helps one to detect among patients with hypertension refractory to treatment those who exhibit controlled blood pressures outside the medical environment, thus permitting one to avoid an unnecessary step-up of treatment. In addition ABPM can also help one to identify symptoms occurring during antihypertensive treatment that are related to excessive drug-induced changes in blood pressure.

The heterogeneity of vascular findings in the kidneys of patients with benign essential hypertension.

As the interlobular arteries of the ageing kidney progressively accumulate intimal fibroplasia, these fibroplastic changes appear to introduce strictures upon the interlobular arteries. These strictures are expected to generate nephron heterogeneity, which is a uniquely disturbed setting peculiarly suited to sustaining both high and low renin forms of hypertension. Fibroplastic renovasculopathy accumulates with age at varying rates in different human populations, and these rates closely parallel the rise of blood pressure with age, as documented by community surveys. Here, I introduce the expression type 1 for hypertension in subjects with mild or minimal renovasculopathy, and type 2 for those with severe vasculopathy. Data reviewed here imply that variations in prevailing blood pressure levels between populations can be attributed entirely, or almost entirely, to type 2 hypertension. No practical test is available to detect nephron heterogeneity clinically. Tests for this purpose have not been and are not now in development. The reason for this deficiency is probably the general lack of suspicion regarding the existence of this pathological entity. Once the entity becomes the target of attention, a variety of tests for measuring its severity in clinical patients should follow readily.

Negative affect, gender, and expressive style predict elevated ambulatory blood pressure in adolescents.

Excessive blood pressure elevations during daily activities increase cardiovascular risk and may be related to individual differences in emotionality and expressive style. Emotional traits and ambulatory blood pressure were measured during a typical school day in 228 Black and White adolescents at risk of developing essential hypertension. Trait affect (depression, anger) predicted prevailing blood pressure levels; this association was moderated by gender, social setting (in classroom vs. with friends), and nonverbal expressive style. Relationships between emotion and blood pressure were not explained by obesity, smoking, or alcohol use. The uniform environment and regimen of the school made it possible to attribute variations in prevailing blood pressure to personality differences involving ways adolescents perceive and negotiate their social world.

Dietary fish oil administration retards blood pressure development and influences vascular properties in the spontaneously hypertensive rat (SHR) but not in the stroke prone-spontaneously hypertensive rat (SHR-SP).

In the present study, we compared the blood pressure in the SHR-SP and in the spontaneously hypertensive rat (SHR) after dietary administration of fish oil from 4 to 17 weeks of age. The retarding influence of dietary fish oils on the development of hypertension was prominent in the SHR (26 mmHg) and not evident in the SHR-SP (8 mmHg). The enhanced development of blood pressure in both the SHR and the SHR-SP is characterised by an elevated maximum contraction in the mesenteric vascular bed to sympathetic nerve stimulation and to injected noradrenaline. In SHR, but not SHR-SP, this maximum contraction was significantly attenuated by dietary fish oil. Likewise, acetylcholine mediated relaxation of the isolated aorta was enhanced in preparations from the SHR but not the SHR-SP. These physiological changes were also associated with a change in the total n-3 polyunsaturated fatty acids (PUFAs) content in vascular tissue, which were inversely proportional to the prevailing blood pressure values seen in all three strains of rat receiving dietary fish oils. Platelet activated thromboxane production was equally depressed in WKY (Wistar Kyoto), SHR and SHR-SP rats. The results indicate that the blood pressure lowering effect of fish oil when administered during the period of development of hypertension is much greater in the SHR than it is in the SHR-SP. Furthermore the lowering of blood pressure by fish oil administration is related to a restoration of normal vascular contraction and normal vascular relaxation, but not related to a suppression of serum thromboxane production.

Identification of a nonendothelial cell thromboxane-like constrictor response and its interaction with the renin-angiotensin system in the aorta of spontaneously hypertensive rats.

Aortic ring preparations from spontaneously hypertensive rats (SHR) and normotensive Wistar Kyoto (WKY) rats were treated with N omega-nitro-L-arginine (NOLA, 10(-4) M). This produced a sustained contraction in preparations from SHR but not WKY rats. A similar contraction in aortic ring preparations from the SHR was produced with methylene blue (10(-5) M) and NG-monomethyl-L-arginine (10(-5) M). The NOLA-induced contraction was reversed with indomethacin (8 x 10(-6) M), ridogrel (10(-5) M) and SQ 29548 (10(-6) M) thus confirming the involvement of thromboxane A2/prostaglandin H2 processes. Subsequent experiments demonstrated that the thromboxane-like contraction was not dependent upon the presence of endothelial cells and occurred in preparations from young, prehypertensive (5 week) and older (17 week) SHRs. The thromboxane-like contraction was markedly suppressed with chronic captopril treatment and reinstated 4 weeks after withdrawal from captopril. The addition of saralasin (10(-6) M) or captopril (10(-6) M) to aortic ring preparations did not suppress the thromboxane-like contractions. The foregoing findings support the presence of a nonendothelial cell thromboxane-like constrictor agent in the aorta of the SHR that is revealed after impairment of nitric oxide production. The activity of the thromboxane-like constrictor process is not tightly linked to prevailing blood pressure, but is reduced with chronic in vivo inhibition of the angiotensin-converting enzyme.

Aberrant baroreceptor mechanotransduction in adult Dahl rats on low-salt diet.

Single fiber, regularly discharging baroreceptors (n = 118) from adult Dahl salt-sensitive (DS) and salt-resistant (DR) rats on a low-salt diet were studied using an in vitro aortic arch-aortic nerve preparation. Pressure thresholds (Pth) and suprathreshold pressure sensitivities (Sth) were determined from responses to slow ramps of pressure. Pressure-diameter relationships measured in each rat were used to transform Pth and Sth values to their mechanical equivalents in terms of aortic wall strain. DS and DR ages were not different (approximately 50 wk). Despite the low-salt diet, DS tail systolic blood pressures were significantly higher than DR by approximately 25 mmHg. Pth averaged 84 mmHg in DR and 97 mmHg in DS. Sth values were similar in DR and DS (average 1.44 and 1.39 spikes.s-1.mmHg-1 in DR and DS, respectively). Increased variance of baroreceptor properties of DS over DR was a prominent finding and necessitated use of nonparametric statistics. The cumulative distribution of Pth values of DS was significantly different from DR, but Sth values were similar. Thus baroreceptor pressure set points are altered in adult DS, but pressure sensitivity per se is not. The differences in pressure parameters were not eliminated by conversion to their mechanical equivalents. Correlation analysis found only weak relationships between Pth and blood pressure for DS and DR (r less than 0.40). Thus in contrast to previous studies in the spontaneously hypertensive rat model, baroreceptors in adult DS on low salt are characterized by elevated variability and a weaker than expected correlation to the prevailing blood pressure in the animal.(ABSTRACT TRUNCATED AT 250 WORDS)

Hemodynamic effects of the arteriolar vasodilators hydralazine, dihydralazine and endralazine in the conscious spontaneously hypertensive rat

The hemodynamic effects of the vasodilators hydralazine, dihydralazine and endralazine were studied in conscious, unrestrained spontaneously hypertensive rats (SHR) equipped for chronic hemodynamic measurements. The arteriolar vasodilators hydralazine (0.3 mg/kg i.a.) and dihydralazine (0.3 mg/kg i.a.) caused a rapid fall in blood pressure and peripheral resistance, lasting up to 24 h in the case of dihydralazine. Immediately after injection, the cardiac output and heart rate were increased significantly. These effects only lasted for 1–2 h. The hemodynamic pattern of the new vasodilator endralazine (0.1-1 mg/kg i.a.) was very similar, with a duration of action similar to that of dihydralazine. The role of baroreceptor reflexes in the early hemodynamic effects of vasodilators was studied by comparing the effects of 0.3 mg/kg hydralazine in baroreflex-denervated and non-denervated SHR. The decrease in blood pressure and peripheral resistance was significantly larger in the denervated SHR, whereas increases in cardiac output and heart rate were almost completely absent in these animals. These data suggest that baroreceptor reflexes oppose the early fall in blood pressure and peripheral resistance induced by vasodilators. However, the activity of the baroreflex seems of very short duration, suggesting a rapid adaptation to the prevailing blood pressure. Moreover, the data show that endralazine is an effective arteriolar vasodilator in conscious SHR.

Influence of electrical stimulation of the posterior hypothalamus on musculocutaneous and renal circulation in anesthetized dogs.

Hypertension and tachycardia were consistently induced by electrical stimulation of the median posterior hypothalamus in dogs under chloralose anesthesia, curarized and artificially ventilated. When renal and femoral vascular beds were perfused at a constant blood flow, the renal perfusion pressure markedly increased, whereas only minor variations of the femoral perfusion pressure occurred. When the renal and femoral vessels were perfused by the heart at the prevailing blood pressure, peri-arterial electromagnetic flow measurements revealed that renal flow decreased and that femoral flow increased during hypothalamic hypertension, both before and after vagotomy. In the same animals, no significant changes of renal or femoral flow occurred during reflexogenic hypertension induced by carotid occlusion. These marked hemodynamic differences between the reflexogenic and the hypothalamic type of hypertension were consistently and repeatedly observed. The indications that baroreflex counter-regulation and ganglionic inhibition due to elevated catecholaminemia contribute to the relative lack of femoral vasoconstriction during hypothalamic hypertension, are discussed.

Human serum dopamine- -hydroxylase. Relationship to hypertension and sympathetic activity.

Serum dopamine-β-hydroxylase activity varied from 3 to 581 units/ml in a group of 168 untreated adults (90 normals, 78 with borderline or overt hypertension). Levels did not correlate with blood pressure or age, but mean values were significantly lower in blacks than they were in whites. Subjects with exceptionally low levels of serum dopamine-β-hydroxylase activity showed normal cardiovascular function and normal β-hydroxylation of an administered synthetic substrate, hydroxyamphetamine. Pronounced blood pressure reduction by antihypertensive drugs did not change serum dopamine-β-hydroxylase activity, and intensive bicycle exercise produced only small and variable increases. Two subjects with severe sympathetic dysfunction, i.e., orthostatic hypotension, showed normal levels of dopamine-β-hydroxylase activity (89-123 units/ml). Serum dopamine-β-hydroxylase activity varied from 450 to 950 units/ml in five subjects with pheochromocytomas and decreased to one-tenth the preoperative level in one subject who underwent curative surgery. Therefore, serum dopamine-β-hydroxylase activity is not a satisfactory index of sympathetic function; moreover, activity levels do not correlate with prevailing blood pressure. Subjects with pheochromocytomas, however, may show increased serum levels of the enzyme, which demonstrates that such tumors can release dopamine-β-hydroxylase.

THE EFFECT OF BLOOD PRESSURE UPON CHEMORECEPTOR DISCHARGE TO HYPOXIA, AND THE MODIFICATION OF THIS EFFECT BY THE SYMPATHETIC-ADRENAL SYSTEM.

The discharge in single‐ or few‐fibre chemoreceptor preparations from the aortic nerve of the cat has been measured, and plotted against the prevailing blood pressure. If the blood pressure is raised mechanically, the relation between these two variables differs from that found when the pressure is raised reflexly or by catechol amines. It is suggested that the sympathetic‐adrenal system may have a significant effect on the sensitivity of chemoreceptors.