Mechanism Of Blood Pressure Elevation Research Articles

Esaxerenone: blood pressure reduction and cardiorenal protection without reflex sympathetic activation in salt-loaded stroke-prone spontaneously hypertensive rats.

Mineralocorticoid receptor (MR) is involved in the mechanisms of blood pressure elevation, organ fibrosis, and inflammation. MR antagonists have been used in patients with hypertension, heart failure, or chronic kidney disease. Esaxerenone, a recently approved MR blocker with a nonsteroidal structure, has demonstrated a strong blood pressure-lowering effect. However, blood pressure reduction may lead to sympathetic activation through the baroreflex. The effect of esaxerenone on the sympathetic nervous system remains unclear. We investigated the effect of esaxerenone on organ damage and the sympathetic nervous system in salt-loaded stroke-prone spontaneously hypertensive rats (SHRSP), a well-established model of essential hypertension with sympathoexcitation and organ damage. Three-week administration of esaxerenone or hydralazine successfully attenuated the blood pressure elevation. Both esaxerenone and hydralazine comparably suppressed left ventricular hypertrophy and urinary albumin excretion. However, renal fibrosis and glomerular sclerosis were suppressed by esaxerenone but not hydralazine. Furthermore, plasma norepinephrine level, a parameter of systemic sympathetic activity, was significantly increased by hydralazine but not by esaxerenone. Consistent with these findings, the activity of the control centers of sympathetic nervous system, the parvocellular region of the paraventricular nucleus in the hypothalamus and the rostral ventrolateral medulla, was enhanced by hydralazine but remained unaffected by esaxerenone. These results suggest that esaxerenone effectively lowers blood pressure without inducing reflex sympathetic nervous system activation. Moreover, the organ-protective effects of esaxerenone appear to be partially independent of its blood pressure-lowering effect. In conclusion, esaxerenone demonstrates a blood pressure-lowering effect without concurrent sympathetic activation and exerts organ-protective effects in salt-loaded SHRSP. Esaxerenone has antihypertensive and cardiorenal protective effects without reflex sympathetic activation in salt-loaded stroke-prone spontaneously hypertensive rats.

Variability of skin microcirculation in case of arterial hypertension from the view of distributional responses of blood flow

The aim of the study. To evaluate individual variability of skin microcirculation (MC) in patients with arterial hypertension (AH) and characteristics of microvascular (MV) reaction to hypotensive impact from the view of blood distribution. Material and methods. Microcirculation of forearm skin in 176 patients with AH stage 2 was studied by laser doppler flowmetry (LDF). All the patients were divided into 2 groups: 1 - with low (n=46) value of MV resistance and 2 - with high (n=130) value of MV resistance. 90 patients out of the total amount (also divided into the same 2 groups - 25 people in the first group and 65 people in the second) had another study of MC after sublingual taking of 20 mg of corinfar. Results. The results revealed controversial MC skin picture with high blood filling of MV canal and reduced MV tone in the first group and high value of MV tone with hemoperfusion limitation in the second group in patients with AH and the same blood pressure (BP). Reduction in the first group can be caused by redistribution of a minute blood volume kept on a high level in the condition of elevated total peripheral resistance (TPR) (the so called central blood bypass). In this case the skin where a part of a cardiac output goes to serves as a depot. Increase of intravascular resistance in the skin of patients from the second group is caused by prevalence of TPR in hemodynamic mechanisms of BP elevation. Whereas constriction of microcirculation vessel is observed not only in the abdominal vessel area (which is the main area responsible for TPR formation) but also in the other areas, particularly in the skin. Corresponding BP decrease in groups of patients under the influence of corinfar was accompanied by bidirectional shifts of MC values: vasodilation in the second group and vasoconstriction in the first group of patients. It happens due to more balanced bloodflow distribution in the vessel areas more responsible for TPR formation as a result of vasodilation under the influence of corinfar.

PLASMA RENIN ASSESSMENT AS THE STRATEGY OF HYPERTENSION MANAGEMENT

The recent interest to plasma renin activity (PRA) is due to the opportunity of antihypertensive therapy choice that is based on the understanding of the interrelation between renin-angiotensin-aldosterone system (RAAS) and mechanisms of water balance mediated by the renal sodium absorption and water retention. PRA is the way to understand the primary mechanism of blood pressure elevation. PRA < 0,65 ng/ml/h indicates the water retention, and hypertension is considered low-renin and «volume-dependent». If PRA is more than 0,65 ng/ml/h hypertension results from excessive renin secretion and RAAS activation.

Arterial hypertension in the view of a patient

Background. At the present time there are no objective methods that enable definition of the mechanisms of blood pressure elevation in a particular patient. Objective. Based on the results of blood pressure and heart rate measures to find new additional features that could help a differentiated management approach. Design and methods. Literature analysis, model formation and analysis, statistical analysis were performed. Results. The new criteria based on the measurements of blood pressure and heart rate are offered. A new way of reporting the results of blood pressure measurements, and a new computer program for analyses observations with the probability characteristics are offered. Conclusions. The present result can be used for the assessment of blood pressure dynamics, and for check-up of the working hypotheses.

Elevated blood pressure management in acute ischemic stroke remains controversial: Could this issue be resolved?

A transient elevated arterial blood pressure is common in acute ischemic stroke and is often associated with a poor prognosis. The underlying mechanisms of blood pressure elevation are not well understood and its management is still unresolved. This article focuses on pathophysiology and management of elevated blood pressure in acute ischemic stroke. There is evidence that the main causes of a transient blood pressure elevation in acute ischemic stroke are the focal cerebral hypoperfusion and the stress responses with neuroendocrine systems activation. Clinical trials have reported that blood pressure lowering in acute ischemic stroke may have detrimental effect, probably because of impaired cerebral autoregulation. However, quantitative assessment of cerebral perfusion has not been performed during emergency blood pressure reduction in acute ischemic stroke. We suggest that ultrasound carotid artery disease evaluation and cerebral hemodynamics monitoring using bilateral transcranial ultrasonography, during blood pressure management in acute ischemic stroke might contribute to maintaining of an adequate penumbral perfusion and prevent infarct enlargement. Such an approach could individualize the antihypertensive treatment in acute ischemic stroke and improve functional outcome. Prospective studies are needed to confirm such a treatment strategy.

Hypothyroidism and hypertension

Hypothyroidism has been recognized as a cause of secondary hypertension. Previous studies on the prevalence of hypertension in subjects with hypothyroidism have demonstrated elevated blood pressure values. Increased peripheral vascular resistance and low cardiac output has been suggested to be the possible link between hypothyroidism and diastolic hypertension. The hypothyroid population is characterized by significant volume changes, initiating a volume-dependent, low plasma renin activity mechanism of blood pressure elevation. This article summarizes previous studies on the impact of hypothyroidism on blood pressure and early atherosclerotic process.

Angiotensin (1‐7) into rostral ventrolateral medulla is enhanced in spontaneously hypertensive rats

BackgroundAngiotensin‐(1‐7) (Ang‐(1‐7)) is recognized as an important mediator of renin angiotensin system. Ang‐(1‐7) is a peptide of ligand for Ang‐(1‐7)‐Mas receptor, and has opposite actions of angiotensin II in the vasculature. In the central nervous system, however, it has been shown that microinjection of Ang‐(1‐7) into rostral ventrolateral medulla (RVLM), one of vasomotor centers of brainstem increased blood pressure in normotensive rats. The aim of the present study was to determine the possible involvement of Ang‐(1‐7) in the RVLM in hypertension.Methods and ResultsIn anesthetized Wistar‐Kyoto (WKY) rats and spontaneously hypertensive rats (SHR), we microinjected Ang‐(1‐7) (100 pmol) and a Mas receptor antagonist (A‐779: 100 pmol) into the RVLM. Microinjection of Ang‐(1‐7) increased blood pressure in both strains. The changes were, however, significantly greater in SHR than WKY rats (13.3 ± 1.3 mmHg, n=7 vs. 6.6 ± 0.8 mmHg, n=5; p<0.05). In contrast, microinjection of a Mas receptor antagonist (A‐779) deceased blood pressure significantly greater in SHR than WKY rats (‐26.4 ± 1.7 mmHg, n=5 vs. ‐13.7 ± 0.8 mmHg, n=5; p<0.05).ConclusionBoth exogenous and endogenous Ang‐(1‐7) in the RVLM are enhanced in spontaneously hypertensive rats. The Ang‐(1‐7)‐Mas receptor pathway in RVLM may contribute to the mechanisms of blood pressure elevation in spontaneously hypertensive rats.

Secondary hypertension: etiology and mechanism of disease

Hypertension afflicts up to 65 million adults in the USA. Although most cases of hypertension are without an underlying cause (i.e., primary hypertension), secondary causes of hypertension should be investigated due to the potential for cure. This article discusses the common causes of secondary hypertension. Furthermore, the etiology, mechanism of blood pressure elevation and treatment are discussed. Through an understanding of the mechanism, diagnosis and treatment of secondary hypertension, physicians can positively influence the associated long-term morbidity and mortality.

Renal antioxidant enzymes and glutathione redox status in leptin-induced hypertension

Previously, we have demonstrated that leptin increases blood pressure (BP) in the rats through two oxidative stress-dependent mechanisms: stimulation of extracellular signal-regulated kinases (ERK) by H(2)O(2) and scavenging of nitric oxide (NO) by superoxide (O(2-.)). Herein, we examined if renal glutathione system and antioxidant enzymes determine the mechanism of prohypertensive effect of leptin. Leptin administered at 0.5 mg/kg/day for 4 or 8 days increased BP and renal Na(+),K(+)-ATPase activity and reduced fractional sodium excretion; these effects were prevented by NADPH oxidase inhibitor, apocynin. Superoxide scavenger, tempol, abolished the effect of leptin on BP and renal Na(+) pump in rats receiving leptin for 8 days, whereas ERK inhibitor, PD98059, was effective in animals treated with leptin for 4 days. Leptin administered for 4 days decreased glutathione (GSH) and increased glutathione disulfide (GSSG) in the kidney. In animals receiving leptin for 8 days GSH returned to normal level, which was accompanied by up-regulation of gamma-glutamylcysteine synthetase (gamma-GCS), a rate-limiting enzyme of the GSH biosynthetic pathway. In addition, superoxide dismutase (SOD) activity was decreased, whereas glutathione peroxidase (GPx) was increased in rats receiving leptin for 8 days. Cotreatment with gamma-GCS inhibitor, buthionine sulfoximine (BSO), accelerated, whereas GSH precursor, N-acetylcysteine (NAC), attenuated leptin-induced changes in gamma-GCS, SOD, and GPx. In addition, coadministration of BSO changed the mechanism of BP elevation from H(2)O(2)-ERK to (O(2-.))-NO dependent in animals receiving leptin for 4 days, whereas NAC had the opposite effect in rats treated with leptin for 8 days. These results suggest that initial change in GSH redox status induces decrease in SOD/GPx ratio, which results in greater amount of (O)2-.)) versus H(2)O(2) in later phase of leptin treatment, thus shifting the mechanism of BP elevation from H(2)O(2)-ERK to (O(2-.))-NO dependent.

Development of the metabolic syndrome along the female biological life-path

Development of the metabolic syndrome along the female biological life-path

Does the AT2-receptor mediate anti-atherosclerotic actions?

Does the AT2-receptor mediate anti-atherosclerotic actions?

Common Genetic Mechanisms of Blood Pressure Elevation in Two Independent Rodent Models of Human Essential Hypertension

Genetic studies of essential hypertension, a complex, polygenic, and age-dependent disorder, have not been able to completely elucidate the genes responsible for development of the trait. We used a novel strategy to compare gene expression in the adrenal gland of two independent rodent models of human essential hypertension (the spontaneously hypertensive rat, SHR, and the blood pressure high mouse, BPH), with the goal of uncovering shared, common genetic mechanisms of hypertension across mammalian species that might, therefore, be pertinent to human hypertension. We deliberately studied young, 4- to 5-week-old, "prehypertensive" SHR and BPH that had not yet developed complete elevations in blood pressure (BP), so that we could minimize the impact of chronic, sustained BP elevation, age, and other confounding factors on gene expression, therefore increasing the likelihood that differential expression reflects relatively early pathogenic mechanisms in hypertension, rather than later responses to, or compensations for BP elevation. We compared transcript expression patterns of genes orthologous between the rat and the mouse, and presented candidate genes for hypertension that are differentially expressed in the same direction in SHR and BPH (ie, overexpressed in both SHR and BPH, or underexpressed in both SHR and BPH). Then we used a systems biology approach to analyze expression patterns in biochemical pathways and networks to isolate systems involved in hypertension pathology in both SHR and BPH. We found transcript pattern evidence for involvement of several systems in the pathology of hypertension in SHR and BPH: adrenal catecholamines and sympathetic function; steroid hormone synthesis, catabolism, and its contribution to enhanced glucocorticoid sensitivity in SHR; oxidative stress and its role as a common mechanism of vascular and end-organ injury; and intermediary metabolism with global but mechanistically different perturbations in SHR and BPH. Approximately 10% of the differentially expressed orthologous genes we studied shared a common direction of expression in the two hypertensive rodent strains, suggesting fundamental transcriptional mechanisms in common whereby mammals can elevate BP or respond to such elevation; even these shared orthologs spanned a diverse set of biological processes, reinforcing the multifactorial and complex nature of hypertension.

Obesity-related hypertension: role of the sympathetic nervous system, insulin, and leptin.

Heightened sympathetic nervous system activity, hyperinsulinemia, insulin resistance, and hyperleptinemia contribute to obesity-related hypertension. However, the precise mechanism and sequence of events in this pathophysiologic event have not been clarified. This review concentrates on studies helping to clarify the mechanisms of blood pressure elevation associated with weight change, concentrating on the temporal changes in neuroendocrine factors that are known to control energy metabolism and blood pressure. A better understanding of the pathophysiologic mechanisms of obesity-related hypertension may help in prevention, treatment, and slowing of the cardiovascular complications of obesity.

A family history of obesity, a family history of hypertension and blood pressure levels

We previously reported that family history (FH) of hypertension (HT) related with stimulated sympathetic activity and BP elevation in nonobese men over 10 years. In addition, it is probable the sympathetic nervous activation with weight gain is a major mechanism of blood pressure elevation. Hyperinsulinemia and hyperleptinemia may be ancillary factors, contributing to sympathetic nervous stimulation with weight. In the present study, we tried to delineate the effects of both family history of obesity (OBFH) and hypertension (HTFH) on BP levels in young men. A positive or a negative OBFH was defined as both parents were obese (BMI > 26.0 kg/m2) or lean (< 22.0 kg/m2). A positive or a negative HTFH were defined as both parents were HT (>140/90 mmHg) or NT (<130/85 mmHg). The subjects were 21 lean OBFH− & HTFH−, 7 lean OBFH− & HTFH+, 8 lean OBFH+ & HTFH−, 5 lean OBFH+ & HTFH+, 9 obese OBFH− & HTFH−, 5 obese OBFH− & HTFH+, 16 obese OBFH+ & HTFH−, 17 obese OBFH+ & HTFH+. They were measured BMI, BP, pulse rate, plasma norepinephrine (NE), insulin, and leptin after overnight fast in supine position. The subjects were men and non-diabetic. Obese subjects had significantly higher levels in BP, NE and insulin than lean subjects regardless of OBFH or HTFH. In OBFH+ regardless of BMI, BP, NE, insulin, and leptin in HTFH+ were higher compared with HTFH−. On the other hand, in OBFH−, BP and NE in HTFH+ were higher than HTFH−, although plasma insulin and leptin in HTFH+ were similar to those in HTFH−. These results demonstrated that OBFH and HTFH contribute BP levels. Sympathetic activation with HTFH is a dominant mechanism in BP elevation, and hyperinsulinemia and hyperleptinemia may be ancillary factors with sympathetic activation in obese subjects and subjects with OBFH.

Weight gain-induced blood pressure elevation.

This study was conducted to evaluate the mechanisms in weight gain-induced blood pressure (BP) elevation focusing, in particular, on the contributions of sympathetic nervous system activity, fasting plasma insulin, and leptin to BP levels. The study design was longitudinal with a cohort of 1897 men. BP, pulse rate, body mass index (BMI), fasting plasma norepinephrine (NE), insulin, and leptin were measured at 6 and 12 months in those 172 lean normotensive, 79 obese normotensive, 64 lean untreated hypertensive, and 38 obese untreated hypertensive men whose BMI increased >10% during the first 6 months. At entry, levels of BP, pulse rate, plasma NE, insulin, and leptin in obese subjects, regardless of BP status, were significantly greater than those in lean subjects. The levels of plasma NE, insulin, and leptin increased with weight gain in the 4 study groups. In the subjects with BP elevation, the increase in pulse rate and plasma NE was significantly greater than that in the subjects without BP elevation at both 6 and 12 months for each of the 4 study groups, although the increase in BMI was similar between the subjects with and without BP elevation. In obese but not lean subjects, whether normotensive or hypertensive, the increases in plasma insulin and plasma leptin with weight gain were greater in the subjects with accompanying BP elevation compared with the subjects without BP elevation. On the other hand, at 6 months in lean subjects, the increase in plasma insulin with weight gain in the subjects with BP elevation was actually lower than that in the subjects without BP elevation. These results suggest that weight gain-induced sympathetic overactivity is more tightly linked to weight gain-induced BP elevation than the changes in plasma insulin and leptin that also accompany weight gain. It is probable that sympathetic nervous activation with weight gain is a major mechanism of blood pressure elevation. Hyperinsulinemia and hyperleptinemia may be ancillary factors that contribute to sympathetic nervous stimulation with weight gain.

Absence of hypertensive retinopathy in a Turkish kindred with autosomal dominant hypertension and brachydactyly

BACKGROUNDA 60 member Turkish kindred with autosomal dominant hypertension, which cosegregates completely with brachydactyly and short stature, was studied. Affected people have severe hypertension and generally die of stroke by...

Hemodynamic effects of short-term noise exposure--comparison of steady state and intermittent noise at several sound pressure levels.

The purpose of the present study was to investigate the extent of blood pressure elevation during noise exposure, to elucidate the underlying hemodynamic mechanisms and to assess baroreceptor cardiac reflex sensitivity in connection with blood pressure elevation. Twenty-two young normotensive males participated in the experiment and underwent six noise exposure conditions of 20 min each: steady state and intermittent pink noises of 80 dB (sound pressure level (SPL)), 90 dB (SPL) and 100 dB (SPL). The results indicate that elevations in mean arterial pressure, as well as diastolic and systolic blood pressure, were significant or almost significant in the intermittent 100 dB (SPL) and 90 dB (SPL) conditions. Habituation occurred particularly with the steady state noises. In at least the intermittent 100 dB (SPL) condition, an increase in peripheral vascular resistance was the underlying hemodynamic mechanism of blood pressure elevation. Decreases in cardiac output and stroke volume were also associated with the peripheral vasoconstriction. Baroreceptor reflex sensitivity was maintained near the baseline level for all of the noise exposure conditions. Therefore, reflex sensitivity may not have been suppressed even in the intermittent 100 dB (SPL) condition during which blood pressure elevations occurred.

Reversal of low dose angiotension hypertension by angiotensin receptor antagonists.

During acute angiotension II (Ang II) infusion (200 ng/kg/min i.v.) into anesthetized rats, mean arterial pressure rose from 124 +/- 1 to 154 +/- 2 mm Hg. The peptidic Ang II antagonist saralasin lowered arterial pressure in a dose-dependent manner. The maximal decrease in pressure was similar to that observed after the Ang II infusion was discontinued. The nonpeptide Ang II antagonist, 4'-[( 2-butyl-4-chloro-5-(hydroxymethyl)-1H-imidazole-1-yl] methyl) [1,1'-biphenyl] -2-carboxylic acid (SC-48742), lowered acutely elevated arterial pressure to a level similar to that on discontinuation of the angiotensin infusion. Chronic (8 days) infusion of Ang II (20 ng/kg/min i.v.) increased mean arterial pressure from 116 +/- 3 to 164 +/- 7 mm Hg, which then decreased to 121 +/- 6 mm Hg on termination of the infusion. Saralasin (10 micrograms/kg/min, a maximally effective dose during acute angiotensin infusion) decreased mean arterial pressure from 168 +/- 7 to 141 +/- 3 mm Hg, a pressure significantly higher (p less than 0.05) than the pressure observed after the angiotensin infusion was discontinued. SC-48742 decreased mean arterial pressure from 167 +/- 7 to 127 +/- 3 mm Hg, a pressure not statistically different from the minimum pressure observed after the angiotensin infusion was terminated. The mechanism of blood pressure elevation during acute high dose or chronic low dose Ang II infusion is different, the latter having a significant neural component as measured by the response to trimethaphan. The peptidic antagonist saralasin was fully effective in lowering acute angiotensin hypertension but only partially effective during chronic hypertension.(ABSTRACT TRUNCATED AT 250 WORDS)

Sodium transport parameters in erythrocytes of patients with primary aldosteronism.

Primary aldosteronism is an uncommon cause of hypertension but one of particular interest because of its distinctive pathophysiological mechanism of blood pressure elevation. Aldosterone has been associated with increased Na+,K+-adenosine triphosphatase (ATPase) activity, but there is controversy over which sodium transport parameters are responsible for this increase. We measured intracellular sodium, ouabain-sensitive and ouabain-insensitive sodium efflux, and the number of Na+,K+-ATPase sites of washed erythrocytes, as well as Na+-Li+ countertransport and the Li+-K+ cotransport rate constant of lithium-loaded red blood cells (RBCs) in six patients with primary aldosteronism and in 50 normal subjects. Ouabain-sensitive sodium efflux was significantly (p less than 0.001) higher for the primary aldosteronism patients than for normal subjects (1.85 +/- 0.29 vs 1.51 +/- 0.21 mmol/L RBC/hr) even though the intracellular sodium concentration (7.2 +/- 1.5 vs 6.7 +/- 1.9 mM) and the number of the Na+,K+-ATPase sites per RBC (331 +/- 52 vs 385 +/- 97) were not increased. The elevated sodium efflux appeared to be due to a significant (p less than 0.001) increase in the rate constant (1.60 +/- 0.12 x 10(-15) vs 1.28 +/- 0.15 x 10(-15) mmol/site/hr) of the ouabain-sensitive sodium efflux. The rate constant decreased significantly (p less than 0.01) after treatment.

Baroreceptor stimulation alters pain sensation depending on tonic blood pressure.

ABSTRACTIt has been hypothesized that activation of the baroreceptor reflex arc, by its central nervous inhibitory effects, is involved in an operant learning mechanism of blood pressure elevation. The present study investigated the effects of mechanical stimulation of the baroreceptors in the carotid sinus on pain threshold and electrical brain activity in two groups of humans with different tonic blood pressure levels. In normotensives, baroreceptor stimulation lowered pain threshold as compared to a control condition, while borderline hypertensives tolerated more intense electric stimulation when baroreceptors were activated. A marked reduction of the contingent negative variation in anticipation of the aversive stimulation accompanied baroreceptor stimulation, probably a consequence of baroreceptor afferent impulses exerted via brainstem centers to cerebral cortex. The distribution of the potential change across the scalp depended on the tonic blood pressure, indicating differences in brain functioning between normotensives and borderline hypertensives.The present results suggest that the hypothesis of an operantly‐conditioned blood pressure elevation under stress may be valid only in subjects with a predisposition for essential hypertension.