Mechanism For Development Of Hypertension Research Articles

Cyclic strain promotes MCP-1 expression in Dahl Salt Sensitive (SS) rat vascular smooth muscle cells (VSMCs) through the TGF-β pathway

Prior studies have suggested a role for TGF-β in the generation of hypertension in SS rats. We have shown that production of MCP-1 (CCL-2) and TGF-β1 increase in the vasculature of hypertensive SS rats. This study aims to explore novel mechanisms of hypertension development. We hypothesize that TGF-β1 regulated the production of MCP-1 by VSMCs in the setting of cyclic strain. Primary cultures of SS aortic VSMCs in early (<6) passages were grown in standard fashion in Dulbecco’s Modified Eagle’s Medium supplemented with 10% fetal bovine serum. Cultured cells were identified as smooth muscle cells by their characteristic morphology and positive immunostaining for α-smooth muscle actin. In the first study, VSMCs were treated with recombinant active TGF-β1 (1 ng/mL and 10 ng/mL) for 6 h, then harvested for MCP-1 mRNA quantification by SYBR green qPCR. Medium was also collected to determine MCP-1 levels using ELISA. TGF-β1 increased MCP-1 mRNA expression by 2.0- and 3.1-fold in VSMC incubated in medium containing 1 ng/mL and 10 ng/mL of TGF-β1, respectively. In a second series of studies, VSMCs were seeded onto 6-well BioFlex plates. Some cells were pre-treated with 10 μmol/mL of an ALK4/5 inhibitor. Cyclic strain, an in vitro model of hypertension, was performed using the FlexCell 6000 and a standardized regimen (8 h, 15% elongation @ 1 Hz). Cells and medium were then harvested for mRNA analyses and determination of MCP-1 levels. When compared with expression by VSMCs maintained under static condition, cyclic strain increased (p<0.05) MCP-1 mRNA expression 4.2-fold and TGF-β1 mRNA 1.93-fold. Cyclic strain also increased (p<0.01) MCP-1 protein in the medium (static condition vs cyclic strain, 112.6 ± 7.1 pg/mL vs 222.5 ± 6.5 pg/mL, n=6). Pre-treatment of VSMC with the ALK4/5 inhibitor reduced mRNA expression of MCP-1 mediated by cyclic strain (Cyclic strain vs Cyclic strain + AKL4/5 inhibitor, 4.5 ± 1.06 vs 2.88 ± 0.47, n=6, P < 0.01). Thus, cyclic strain promotes MCP-1 production by VSMCs through the TGF-β pathway. The data support the need for further study of this interaction as well as a potential role in arterial hypertension in this rodent model. Department of Veterans Affairs Basic Sciences R&D (BSRD) Service (1 I01 BX005640) National Institutes of Health (P30 DK079337). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Blood pressure regulation and mechanism of hypertension development in dogs and cats: A review

The review article aims at discussing the mechanisms of blood pressure regulation and hypertension development in dogs and cats. This will enhance the knowledge of clinicians and researchers on the pathophysiology of hypertension and mechanisms of normal blood pressure regulation in small animals. Hypertension is a risk factor for other cardiovascular diseases in man and animals, however, most small animal clinicians do not routinely check the blood pressure until the animals are presented with complications. Hypertension in animals can be essential or secondary but the secondary type is predominant. Blood pressure is regulated by vasoactive agents and hormones such as nitric oxide, bradykinin, endothelin-1, angiotensin II and aldosterone. The blood vessels and the kidney also play major roles in blood pressure regulation. Alterations in the regulation frameworks result in hypertension and cardiovascular diseases as elucidated in this review article. It is therefore essential that the body maintain good anatomic, physiologic and biochemical functions to maintain blood pressure. In conclusion, adequate knowledge of the mechanism by which blood pressure is regulated and the pathophysiology of hypertension will enhance research and potentiate the management of cardiovascular diseases and associated disorders in small animals.

Serum macrophage colony-stimulating factor levels in patients with essential hypertension after vaccination against SARS-CoV-2

The formation of immunity in the population to various variants of the COVID-19 pathogen is one of the most important problems for the world community. The aim of the study was to compare the dynamics of M-CSF and VEGF-A, IL-34 in the blood serum of patients with essential hypertension (EH) stage II, depending on the type of immunity formed (post-infectious, post-vaccination, “hybrid”) to analyze changes of M-CSF-mediated mechanisms of hypertension development. During the work, 2 groups of patients were formed: group 1-patients with stage II EH and SARS CoV-2 infection without pneumonia in the anamnesis, vaccination 6 months after laboratory recovery, group 2 – patients with stage II EH without COVID-19 in the anamnesis, vaccination during the follow-up period. Determination of M-CSF, IL-34, VEGF-A, IgG level to SARS-CoV-2 was determined using an enzyme-linked immunosorbent assay. The formation of post-infectious immunity in patients with stage II EH, despite the mild course of COVID-19, is accompanied by a long-term (up to 6 months) pathophysiologically significant increase in the serum level of M-CSF (p 0.001) with a decrease in IL-34 (p 0.001). Analysis of the dynamics of changes in M-CSF, IL-34, VEGF-A in the postvaccination period in the blood serum of patients with stage II EH with COVID-19 in the anamnesis (“hybrid” immunity), determined the absence (p 0.05) of changes in the levels of M-CSF, VEGF-A after the first component of “SPUTNIK V” against the background of an increase of the level of IgG to SARS-CoV-2. 21 days after the second component of the vaccine, an increase of M-CSF was detected when compared with both pre-vaccination indicators and data 21 days after the introduction of the first component of the vaccine (p 0.001). Comparing the dynamics of the of M-CSF, IL-34 and VEGF-A in patients with stage II EH without COVID-19 in the post-vaccination period with the data on the formation of “hybrid” immunity, an increase in M-CSF was recorded 21 days after the introduction of the first and second components against the background of a decrease in IL-34, but with the restoration of pre-vaccination concentrations in 100% of patients by day 180 with comparable immunogenicity after 180 days. In patients with EH II, the pathogenetic “summation” of the pre-infectious imbalance of cytokine regulation and postcovid changes is important, which in a number of patients may be the reason for the prolongation of the stabilization of the balance of the M-CSF-IL-34-VEGF-A system in the post-vaccination period during the formation of “hybrid” immunity.

Association between hypertension, obesity and dietary intake in post-menopausal women from rural Zambian communities.

BackgroundAmongst the cardiovascular risk (CVR) factors, hypertension (HT) and obesity appear to be prominent in post-menopausal women. The underlying mechanisms of HT development in menopause are not fully understood.AimTo determine the association between HT, obesity and dietary intakes in post-menopausal women from rural Zambia.SettingThis study was conducted in Twatasha Compound of Kitwe and Ndeke Community of Ndola.MethodsBlood pressure (BP), weight, height and dietary intakes (24-h recall) were measured in 153 women (> 50 years) from households. The South African Hypertension Society (SAHS), the World Health Organization (WHO) and estimated average requirements (EARs) guidelines were followed for HT, obesity and dietary intake definitions, respectively. Statistical Package for the Social Sciences (SPSS) version 26 was used for descriptive and inferential statistical analyses.ResultsPrevalence of HT was 70%, whilst 37.25% and 28.10% of the participants were overweight and obese, respectively. The median interquartile range (IQR) dietary intakes showed inadequate intakes for most nutrients, except for carbohydrates (170 g [133; 225]). The total fat intake represented 14% of total energy intake. All median fatty acid intakes and sodium intakes (409 mg [169; 662]) were below the recommended levels. Only body mass index (BMI) correlated with HT (r = 0.268; p = 0.001).ConclusionsDespite low dietary intakes, an alarming prevalence of HT and obesity was found in our population. Hormonal changes, a high energy-dense diet and poor treatment adherence, may be possible underlying factors. We recommend measures to better manage HT as a CVR factor.ContributionThis article supplements evidence on the prevalence of obesity-related hypertension in post-menopausal women and the link to dietary intake.

Function of Perivascular Nerves in Insulin Resistance-induced Hypertension

Many patients with type 2 diabetes mellitus develop hypertension, although the actual mechanism remains unknown. To clarify possible mechanisms of hypertension development in diabetes, this study investigated the acute or chronic influence of hyperinsulinemia and/or hyperglycemia on the function of perivascular nerves, which play a critical role in vascular tone regulation. Acute hyperinsulinemia in euglycemic pithed rats, which had no autonomic flow, significantly augmented adrenergic nerve-mediated pressor responses and inhibited calcitonin gene-related peptide (CGRP)-containing (CGRPergic) nerve-mediated depressor responses. To increase blood glucose levels without changing serum insulin levels, pithed rats were treated with octreotide. In this model, acute hyperglycemia produced only marked enhancement of adrenergic nerve-mediated vasoconstriction. Chronic hyperinsulinemia in insulin resistance model rats caused significant increases in the function and distribution of perivascular sympathetic nerves and decreases in those of perivascular CGRPergic nerves, resulting in the development of hypertension (insulin resistance-induced hypertension). Treatment with pioglitazone or functional foods with an insulin resistance-improving effect prevented the development of insulin resistance-induced hypertension. The present studies suggest that acute and chronic hyperinsulinemia reduces vasodilator function of perivascular CGRPergic nerves and enhances the vasoconstrictor function of perivascular adrenergic nerves, leading to the development of hypertension. The results also indicate that hyperinsulinemia and hyperglycemia may have a crucial role in the alteration of neuronal vascular tone regulation.

Effect of Uric Acid-Lowering Agents on Endothelial Function: A Randomized, Double-Blind, Placebo-Controlled Trial.

Higher levels of serum uric acid are independently associated with endothelial dysfunction, a mechanism for incident hypertension. Overweight/obese individuals are more prone to endothelial dysfunction than their lean counterparts. However, the effect of lowering serum uric acid on endothelial dysfunction in these individuals has not been examined thoroughly. In this randomized, double-blind, placebo-controlled trial of nonhypertensive, overweight, or obese individuals with higher serum uric acid (body mass index ≥25 kg/m2 and serum uric acid ≥5.0 mg/dL), we assigned subjects to probenecid (500-1000 mg/d), allopurinol (300-600 mg/d), or matching placebo. The primary outcome was endothelium-dependent vasodilation measured by brachial artery ultrasound at baseline and 8 weeks. By the end of the trial, 47, 49, and 53 participants had been allocated to receive probenecid, allopurinol, and placebo, respectively. Mean serum uric acid levels significantly decreased in the probenecid (from 6.1 to 3.5 mg/dL) and allopurinol groups (from 6.1 to 2.9 mg/dL) but not in the placebo group (6.1 to 5.6 mg/dL). None of the interventions produced any significant change in endothelium-dependent vasodilation (probenecid, 7.4±5.1% at baseline and 8.3±5.1% at 8 weeks; allopurinol, 7.6±6.0% at baseline and 6.2±4.8% at 8 weeks; and placebo, 6.5±3.8% at baseline and 7.1±4.9% at 8 weeks). In this randomized, double-blind, placebo-controlled trial, uric acid lowering did not affect endothelial function in overweight or obese nonhypertensive individuals. These data do not support the hypothesis that uric acid is causally related to endothelial dysfunction, a potential mechanism for development of hypertension.

Chronic effects of obstructive apnea on renal and lumbar sympathetic nerve activity in conscious rats (857.3)

This study investigated responses of renal (RSNA) and lumbar sympathetic nerve activity (LSNA) of rats to repeated obstructive apnea over 4 days. Wistar male rats were chronically instrumented for measurements of RSNA, LSNA, and oxygen saturation of the brain tissue, and a tracheal balloon for induction of apnea was implanted. At least 3 days after the surgery, the rats were subjected to obstructive apnea by inflating the tracheal balloon for 40 seconds. This process was repeated 6 times/hour for 5 hours/day over a 4‐day period. The basal level of RSNA increased gradually and significantly throughout the 4‐day experimental period. The magnitude of the LSNA increase was less than that of RSNA. The basal levels of arterial pressure and heart rate remained within the normal ranges throughout the experimental period. These data suggest that repeated obstructive apnea activates RSNA in a cumulative manner, which may in part explain the underlying mechanism for development of hypertension in sleep apnea syndrome. JSPS Grant.

Searching for genes involved in hypertension development in special populations: children and pre-eclamptic women. Where are we standing now?

Primary hypertension is a very common disorder particularly in the aging population but hypertensive disorders can appear earlier in life, especially when obesity and unhealthy lifestyle are present. Also pregnant women can be at risk of developing gestational hypertension and/or pre-eclampsia, which causes complications in nearly 7% of pregnancies. These "special" populations could be regarded as natural models suited to reveal mechanisms of hypertension development which are either common to other forms of hypertension, including primary hypertension or specific to these populations. Recent studies in the field of genetics of primary hypertension have used new powerful tools, such as genome-wide association studies (GWAS) and sequencing, but studies about hypertension during childhood and in pregnancy have seldom used high-throughput technologies and the knowledge in this field comes mostly from the candidate gene approach. In this review we summarize some interesting results from genetic studies conducted in childhood and adolescence and during pregnancy and underline the need to apply modern technologies in these potentially very fruitful populations.

Gender Differences in the Effects of Angiotensin Receptor Blockers on Cardiovascular Disease

Women tend to develop hypertension later as they transition into menopause, and during and after menopause the development of hypertension in women is independent of age and body mass index (BMI) but is related to menopause itself. One of the mechanisms of hypertension development in postmenopausal women is believed to be the lack of estrogen leading to vasoconstriction due to both renin-angiotensin-aldosterone (RAA)-sensitive and sodium-sensitive pathways. Nowadays, we have many medications of antihypertensive therapy, including angiotensin converting enzyme (ACE) inhibitor and angiotensin receptor blocker (ARB) in addition to diuretics, beta-blockers, calcium channel blockers. The present review summarizes gender differences in the effects of ARB on blood pressure lowering and cardiovascular outcomes from the published reports of large-scaled, randomized clinical trials and its substudy on sex-specific difference. Many antihypertensive drugs have been developed, and the benefit of blood pressure lowering therapy for the prevention of cardiovascular disease would be expected not only in men but also in women as indicated in the large-scaled clinical studies with ARB.

The Functional Changes of the Perivascular Adipose Tissue in Spontaneously Hypertensive Rats and the Effects of Atorvastatin Therapy

The aim of this study was to examine the function of perivascular adiposa tissue (PVAT) on vascular relaxation response in spontaneously hypertensive rats (SHR) and the modulatory effects of the atorvastatin therapy on the PVAT functions. We investigated the mechanisms of the perivascular adipocyte-derived relaxation factor (PVRF) by using isolated rat's aortic rings and isometric contraction measurements. We found that contraction of the thoracic aorta induced by phenylephrine was significantly attenuated in the presence of PVAT from normotensive Wistar-Kyoto rats (WKY group) or the spontaneously hypertensive rats treated with atorvastatin (SHR-A group, atorvastatin 50mg/kg/day), whereas this effect was not observed in the thoracic aortic rings from the control SHR (SHR group). Transferring the solution incubated with PVAT-intact thoracic aorta to PVAT-free thoracic aorta, it induced a remarkable relaxation response in the WKY but not in the control SHR. Tetraethylammoniumchloride (TEA) could block the above relaxation. It was also shown that the PVRF function was likely, depending on the extracellular [Ca2+]; the anti-contractile effect of PVAT could be reduced by the inhibitor of the adenosine triphosphate (ATP)-dependent potassium channels, glibenclamide, and could be reduced by the inhibitor of cyclooxygenase by indomethacin. We thus infer that the PVAT function was distorted in hypertension rats, and the lipid-lowering treatment with atorvastatin could restore the PVAT function. The function of the PVRF may involve the Ca2+-activated potassium channels, the ATP-dependent potassium channels in vascular smooth muscle cell (SMC), and the release of PVRF from PVAT may involve prostaglandins (PGs) and the calcium metabolism. These results provide an insight into the pathological mechanisms of hypertension development, and indicate that the PVAT may be a potential new target for the hypertensive therapy.

The underlying mechanisms for development of hypertension in the metabolic syndrome

The underlying mechanisms for development of hypertension in the metabolic syndrome

The underlying mechanisms for development of hypertension in the metabolic syndrome

High blood pressure is an important constituent of the metabolic syndrome. However, the underlying mechanisms for development of hypertension in the metabolic syndrome are very complicated and remain still obscure. Visceral/central obesity, insulin resistance, sympathetic overactivity, oxidative stress, endothelial dysfunction, activated renin-angiotensin system, increased inflammatory mediators, and obstructive sleep apnea have been suggested to be possible factors to develop hypertension in the metabolic syndrome. Here, we will discuss how these factors influence on development of hypertension in the metabolic syndrome.

Inhibitory Effects of Dynorphin-A on Norepinephrine Uptake by Cardiac Synaptosomal-Mitochondrial Fractions

The effect of dynorphin A-(1-13) (Dyn A-(1-13)) on [3H]norepinephrine ([3H]NE) uptake was examined in cardiac synaptosomal-mitochondrial fractions of control rats (Wistar, WR; Wistar-Kyoto, WKY) and spontaneously hypertensive rats (SHR). In adult WR, Dyn A-(1-13) caused naloxone-insensitive dose-dependent inhibition of [3H]NE uptake with an IC50 of 4.0 microM. The nonopioid Dyn A fragments Dyn A-(2-13) and Dyn A-(6-10) displayed 89 and 11% of the potency of Dyn A-(1-13), respectively, whereas Dyn A-(1-8), Leu-enkephalin, and the selective opioid agonists [D-Ala2, N-MePhe4, Glyol5]enkephalin (DAGO, mu), [D-Ser2, Thr6]Leu-enkephalin (DSLET, delta), and U-50488H (kappa) were inactive. The relative potency of various analogues and fragments of Dyn A in inhibiting [3H]NE uptake correlated well (r = 0.96) with their potency in inhibiting binding of [3H]Dyn A-(1-13) to nonopioid sites on cardiac membrane preparations. Dyn A-(1-13) showed the same potency in inhibiting [3H]NE uptake in prehypertensive (4-week-old) SHR as in age-matched WR and WKY. However, at ages 8 and 16 weeks Dyn A-(1-13) was twice as potent in SHR as in WR and WKY. The increased inhibitory potency of Dyn A-(1-13) in 8-week-old SHR was accompanied by a 1.3-fold increase in number of cardiac nonopioid [3H]Dyn A-(1-13) binding sites. Dyn A and related peptides inhibit [3H]NE uptake by cardiac synaptosomes by a nonopioid mechanism. The possible involvement of such a mechanism in development of hypertension in SHR is discussed.

Cellular selectivity of aldosterone action: role of 11 beta-hydroxysteroid dehydrogenase.

Mineralocorticoid receptors in the distal nephron have no intrinsic specificity for mineralocorticoids over glucocorticoids (cortisol in humans; corticosterone in rodents), but are protected from glucocorticoids by the enzyme 11 beta-hydroxysteroid dehydrogenase, which inactivates these steroids to cortisone and 11-dehydrocorticosterone, respectively. Recent work has demonstrated that the enzyme is expressed as multiple tissue-specific isoforms, some of which catalyse the reverse conversion of cortisone to cortisol. These isoforms may allow 11 beta-hydroxysteroid dehydrogenase to modulate access of ligands to glucocorticoid and mineralocorticoid receptors, as well as to amplify and attenuate tissue responses. 11 beta-hydroxysteroid dehydrogenase-mediated protection of mineralocorticoid receptors fails in congenital 11 beta-hydroxysteroid dehydrogenase deficiency and after inhibition of the enzyme by liquorice. In these circumstances, cortisol-dependent mineralocorticoid excess and hypertension ensue. Recent studies suggest that similar deficiencies of 11 beta-dehydrogenase activity may contribute to pathophysiology in common clinical syndromes, illustrating the potential significance of this novel mechanism for development of hypertension.

Living with High Blood Pressure:

Two experts from the Mayo Clinic, Rochester, Minn, have prepared a highly readable and practical cookbook for the dietary management of persons with high blood pressure. Because hypertension manifests itself in familial clusters, the approach focuses on food preparation for all family members. The potential for carry-over of a dietary life style to other family members may have prophylactic benefits. Nutritional intervention in the form of weight control and regulation of sodium intake is imperative prior to the initiation of drug therapy for control of hypertension. Even if drugs are necessary for control of hypertension, daily regulation of sodium and energy intake are essential adjuncts to total patient management. Organized in three parts, the book presents a brief section defining the physiologic mechanism for development of hypertension, a rationale for its medical management, both drug and dietary, and descriptive menu plans for regulation of sodium intake to 40 and 90

Living With High Blood Pressure: The Hypertension Diet Cookbook

Two experts from the Mayo Clinic, Rochester, Minn, have prepared a highly readable and practical cookbook for the dietary management of persons with high blood pressure. Because hypertension manifests itself in familial clusters, the approach focuses on food preparation for all family members. The potential for carry-over of a dietary life style to other family members may have prophylactic benefits. Nutritional intervention in the form of weight control and regulation of sodium intake is imperative prior to the initiation of drug therapy for control of hypertension. Even if drugs are necessary for control of hypertension, daily regulation of sodium and energy intake are essential adjuncts to total patient management. Organized in three parts, the book presents a brief section defining the physiologic mechanism for development of hypertension, a rationale for its medical management, both drug and dietary, and descriptive menu plans for regulation of sodium intake to 40 and 90