Int J Curr Pharm Res, Vol 13, Issue 6, 1-10Review Article



Department of Pharmacology, CT Institute of Pharmaceutical Sciences, CT Group Institutions, Jalandhar, India 144020
Email: [email protected]

Received: 04 Aug 2021, Revised and Accepted: 10 Oct 2021


The objective of the review is to explain the pathophysiology, different causes and various treatments involved in hypertension. This article discusses the disease's pathogenesis, etiology, diagnosis, and immunity. This review looks at the main significant epidemiological and clinical studies on the role of several lifestyle factors in hypertension development. This review examines the numerous mechanisms that cause hypertension in order to discover new treatments. In addition, it covers the many types of hypertension therapy. According to different studies, lifestyle habits may have an impact on blood pressure levels.

Moreover, the importance of chronic inflammation in hypertension and its repercussions has been confirmed in genetically engineered mice lacking components of innate and/or adaptive immunity. Immune cell depletion enhances endothelial function, lowers oxidative stress, lowers the vascular tone, and protects against renal interstitial infiltrates, salt retention, and kidney injury. Based on existing literature, there is strong evidence that lifestyle variables can affect blood pressure levels. Then, in hypertensive people, lifestyle changes can help by lowering overall cardiovascular risk and death from any cause. The involvement of immunity as a common thread in the hypertension processes of many organ systems.

Keywords: Hypertension, Immune system, Treatment


Hypertension has been recognized by the World Health Organization (WHO) as one of the most important risk factors for morbidity and mortality worldwide, accounting for roughly nine million deaths each year [1]. Essential hypertension (also known as primary hypertension or idiopathic hypertension) is the most prevalent kind of hypertension, affecting 95 percent of hypertensive patients [2-5] and is thought to be caused by a combination of environmental and hereditary factors. Essential hypertension is more common as people become older, and people who have moderately high blood pressure at a young age are more likely to acquire hypertension later in life, which causes them a lot of pain. Hypertension raises the risk of stroke, heart attack, and kidney failure [6]. Hypertension is linked to a higher risk of stroke (both ischemic and hemorrhagic), myocardial infarction, heart failure, chronic renal disease, peripheral vascular disease, cognitive impairment, and early mortality [7].


HTN is divided into two types: primary (or essential) HTN and secondary (or secondary) HTN, which account for 95 percent and 5% of hypertension patients, respectively [8]. Although the cause of essential HTN is unknown, it usually appears in the fifth or sixth decade of life, is frequently related with increasing salt intake and obesity, and has a strong link to family history, suggesting a hereditary predisposition [9]. Secondary HTN is accompanied by recognizable causes such as renal artery stenosis, chronic kidney disease, sleep apnea, and adrenal illnesses [8]. Multiple mechanisms involved in the maintenance of normal blood pressures are disrupted in both scenarios, and as a result, the sympathetic nervous system, renin-angiotensin-aldosterone system, endothelial function, sodium and water retention have all been extensively studied to determine mechanisms involved in the disease's development [10, 11].


Blood pressure rises in youth have been linked to etiological factors linked to hypertension in adulthood. Intrauterine malnutrition, a family history of hypertension, obesity, especially excess abdominal fat, insulin resistance, high dietary sodium intakes, low dietary intakes of calcium, potassium, and magnesium, physical inactivity, high alcohol intakes, tobacco use, drug use (e. g., cocaine, ecstasy, anabolic steroids), emotional stress, diet pill use, and oral contraceptives are some of the factors linked to hypertension [2, 12, 13]. Inadequate nutrition may cause changes in the structure and metabolism of the foetus, increasing the risk of hypertension and other disorders later in life [14]. Hyperinsulinemia and insulin resistance are also linked to the development of hypertension, which can cause a slew of issues. Sodium sensitivity may be caused by high plasma insulin levels [2, 15]. Adequate intakes of potassium, calcium, and magnesium in the diet have been linked to lower blood pressure in children and adolescents. Intakes of potassium and calcium are below recommended limits, especially in adolescent females, but phosphorus and protein intakes, which accelerate calcium loss, are high [16]. Lack of physical activity has been shown to increase the risk of hypertension by 20 to 50 percent.

Risk factors

Individuals with a personal family history of hypertension are more likely to acquire hypertension [17]. Essential hypertension is four times more common in black people than in white people, progresses more quickly, and is often more severe in black patients, with a higher fatality rate. Salt restriction, like diuretic therapy, breaks the pathophysiologic sequence of events by lowering the extracellular fluid volume and blood pressure [18-21]. Obesity can increase the risk of hypertension by fivefold when compared to normal weight, and excess weight is responsible for up to two-thirds of hypertension cases. More than 85 percent of instances occur in those who have a BMI of more than 25 [22]. Another risk factor is salt sensitivity, which has attracted the most attention as an environmental issue. Sodium consumption affects around one-third of the essential hypertensive population [23]. Enhanced sodium ion concentration promotes ADH and thirst processes, resulting in increased water reabsorption in the kidneys, concentrated urine, and increased thirst with increased water consumption. In comparison, water flow between cells and the interstitium performs a small effect. The link between salt consumption and blood pressure is debatable. Although lowering sodium intake lowers blood pressure, the magnitude of the effect is insufficient to propose a widespread salt decrease [24].

Treatment of hypertension

Both non-pharmacologic and pharmacological treatments are used to treat hypertension. Whether or not there is a pre-existing CV, DM, or CKD influences the treatment selection. The 2017 AHA/ACC guideline advocated calculating the 10 y risk of cardiovascular disease for patients with stage one hypertension who did not have these comorbidities. If the risk is less than 10%, it is reasonable to undertake lifestyle changes on their own for 3 to 6 mo. Both lifestyle adjustment and medicine are suggested for stage 2 hypertension with pre-existing conditions such as diabetes mellitus (DM), CKD, and a 10 y risk of CV event of 10% or higher.

Non-pharmacological treatment

Following are the non-pharmacologic way to treatment of hyper-tensions.

Dietary salt restriction

Dietary sodium consumption is limited to less than 1500 mg per day [25, 26]. Dietary salt restriction is related with a reduction of 5 to 10 mmHg in systolic blood pressure and 2 to 6 mmHg in diastolic blood pressure in general hypertensive patients.

Weight loss

If a patient is overweight or obese, weight loss offers a clear advantage in terms of lowering blood pressure and reducing the number of recommended medicines [27]. Long-term weight loss studies have shown that a 10 kg weight loss is connected with a 6 mmHg systolic BP reduction and a 4.6 mmHg diastolic BP reduction.

Physical activity

Regular aerobic exercise reduced systolic blood pressure by 4 mmHg and diastolic blood pressure by 3 mmHg on average. As a result, patients are advised to exercise for 90 to 150 min per week [28, 29]. As a result, all hypertension patients are recommended to exercise.

High fiber and low-fat diet

Dietary approach to halt hypertension (DASH) lowered systolic BP in hypertension patients by 11.4 mmHg and diastolic BP by 5.5 mmHg by consuming a diet rich in fruits and vegetables, potassium, magnesium, calcium, high in low-fat diet and low in saturated fat [30]. A diet rich in fruits and vegetables not only lowers blood pressure but also improves endothelial function.

Pharmacological treatment

The 2017 ACC/AHA guideline advised that antihypertensive medication treatment be started with two first-line drugs from distinct classes, either separately or in a fixed-dose combination, with a target blood pressure of less than 130/80 mmHg [31].

Initial drug selection

Angiotensin-converting enzyme inhibitors (ACE inhibitors), angiotensin receptor blockers (ARBs), calcium channel blockers (CCBs), and thiazide type diuretics are the four types of antihypertensive medications, and each class of antihypertensive drugs reduces CV events [32]. Except for the major effect of beta blockers administered after MI reducing CAD event and calcium channel blockers reducing stroke, a meta-analysis of 147 randomised controlled trials of 464,000 patients with hypertension found that all major antihypertensive drug classes (diuretic, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, beta-blockers, and calcium channel blockers) reduced stroke [33]. The 2011 ACC/AHA hypertension guideline states that the efficacy, tolerability, existence of certain comorbities, and cost of antihypertensive medications in the treatment of adult hypertension are all factors to consider [34]. According to the 2011 ACC/AHA hypertension guidelines, diuretics, ACE inhibitors, ARBs, Beta blockers, and calcium channel blockers (CCBs) may be used to treat older patients with primary hypertension [34].

Hypertension and diabetes mellitus

ACE inhibitors or ARBs, CCBs, and thiazide diuretics should be used to treat patients with hypertension and diabetes [31, 35, 36]. Initial treatment with ACE inhibitors or ARBs in individuals with diabetes mellitus, hypertension, and chronic albuminuria [31, 37, 38].

Hypertension and pregnancy

ACE inhibitors, ARBs, direct renin inhibitors, and atenolol should not be used by pregnant women with hypertension [31, 39-41]. In patients with hypertension during pregnancy, Methyldopa, Hydralazine, Nifedipine, and Labetalol are the drugs of choice [31, 42].

Adverse pathophysiological effects of a wrong lifestyle

Salt intake

The link between sodium consumption and extracellular fluid volume, arterial pressure, and the neuroendocrine system is well understood [43]. Experiments have shown that high salt intake causes an increase in left ventricular mass and intima-media thickness of major arteries, as well as severe proteinuria and renal fibrosis, regardless of arterial pressure [44-48]. Increases in circulating endothelin-1, a potent vasoconstrictor and proinflammatory peptide, are associated with an increase in sodium consumption [49, 50], whereas salt reduction is associated with improvements in artery flow-mediated dilation [51, 52]. The intrinsic action of sodium on microvascular vasomotion could then account for many of the renal and cardiovascular impairments seen in salt-sensitive hypertension individuals. In terms of the function of dietary salt intake in the development and treatment of hypertension, multiple prospective and outcome trials have shown that a lower salt intake is linked to a decreased risk of cardiovascular disease (CVD). The Inter-national Study of Salt and Blood Pressure (INTERSALT) and the Dietary Approach to Stop Hypertension trial (DASH), among other large cohort studies, found a substantial inverse connection between salt intake and both systolic and diastolic blood pressure. Multivariate analysis revealed that a sodium intake of 100 mmol/die resulted in an average increase of 3-6 mmHg in systolic and diastolic blood pressure of 3-6 mmHg in the entire studied group in the INTERSALT investigation, an international multicentre trial [53].

Cigarette smoke

Because of the effects of several substances, particularly nicotine and carbon monoxide, cigarette smoking is widely regarded as a major cardiovascular risk factor for the heart and blood vessels [54, 55]. As a result of nicotine and carbon monoxide activity, functional and structural changes are frequently reported [56-59]. Some research [60-63] found that cigarette smokers had higher blood pressure and develop hypertension than non-smokers, implying that smoking has a negative effect on pressure values related to long-term exposure and the quantity of cigarettes smoked daily. A considerable improvement in systolic and diastolic pressure was recently reported in people who quit or reduced their tobacco intake [64].

Alcohol intake

The harmful effects of alcohol consumption on the liver, heart, pancreas, blood pressure, and other organ systems are well established. The acute effects of alcohol on blood pressure are complex and nonlinear, with pressor and depressor effects varying with time since ingestion [65]. Heavy drinking has long been linked to high blood pressure [66], and studies have found a linear association between alcohol intake, blood pressure levels, and the prevalence of hypertension in the general population [67-69]. Fuchs et al. found that alcohol misuse raises blood pressure, particularly systolic values and that this is more noticeable in black men, regardless of the type of drink consumed, whether red wine, white wine, beer, or liquor [70]. The role of moderate alcohol use, on the other hand, is still being contested. Furthermore, moderate alcohol use has been shown to enhance insulin sensitivity [71, 72] and is linked to a lower risk of developing type 2 diabetes when compared to abstention and heavy drinking [73].

Physical activity

Exercise training has been shown to have many hemodynamic and metabolic benefits, lowering overall cardiometabolic risk. In response to psychophysical stress, it lowers sympathetic responses and has an effect on the hypothalamic-pituitary-adrenal axis, resulting in lower cortisol levels, decreased cardiovascular reactivity, and faster cardiovascular recovery. Furthermore, physical activity causes a systemic adaptation of the artery wall, which may result in a reduction in peripheral resistance [74]. By boosting a number of pro-angiogenic factors, exercise training increases the number of capillaries for muscle fibre [75, 76]. It has also been observed [77-79] that regular physical activity can prevent hypertension from developing, with sedentary normotensive persons having a relative risk of hypertension of 35 percent to 70 percent higher than their physically active peers. Furthermore, regular aerobic exercise training has been found to improve lipid profile, glycemic management, and obesity, lowering global cardiovascular risk and mortality [80, 81]. As a result, current European and American standards strongly urge moderate-intensity dynamic aerobic exercise for at least 30 min on 5-7 d each week [82, 83].

Dietary patterns

The impact of changing entire eating habits on blood pressure has been studied extensively. A variety of research suggests that, in addition to reducing alcohol and salt intake, adopting an optimal diet plays a role in lowering blood pressure values. Although calorie consumption is linked to body weight, obesity and overweight are linked to hypertension. Weight loss decreases blood pressure irrespective of achieving a desirable body weight, according to studies [84-86]. An average weight loss of 5.1 kg was linked to a drop in mean 4.4 mmHg systolic and 3.6 mmHg diastolic pressure in a meta-analysis of 25 trials [27].

Modest weight loss has also been shown to reduce hypertension in pre-hypertensive people and to make medication reduction and discontinuation easier [87-89]. Increased potassium intake has been shown to reduce blood pressure in both non-hypertensive and hypertensive participants [30, 90, 91]. This potassium hemodynamic effect appears to be more significant in people who consume a lot of sodium, and it could be linked to potassium-mediated sodium excretion in the distal renal tubule [30].

Omega-3 polyunsaturated fatty acids, which are mostly found in fish, have been shown to reduce the incidence of cardiovascular disease, implying that eating more fish is beneficial [92]. Omega-3 supplementation has also been shown to enhance arterial stiffness and endothelial function [93]. The ability of omega-3 fatty acid to incorporate into phospholipid membranes, partially replacing arachidonic acid as an initial substrate for the production of anti-inflammatory eicosanoids, is thought to be the cause of these effects. Furthermore, some studies [94-96] found a small but significant reduction in blood pressure in patients taking omega-3 supplements. A meta-analysis that included 8 studies with over 56,000 participants recently found that normotensive people who consumed the most omega-3 in their diet had a 27 percent lower chance of developing hypertension than those who consumed the least [97].

Increased antioxidant qualities have been linked to olive oil use. Extra virgin olive oil contains antioxidants, free radical scavengers, and enzyme modulators such as phenolic compounds, hydroxytyrosol, and oleuropein [98].

Table 1: Effects of a poor lifestyle on the body's pathophysiology

Heavy alcohol intake Liver, pancreas and cardiovascular damage
Excessive salt consumption

Circulation volume has increased

Increased mass of the left ventricle

Thickness of the intima-media has increased

Plasma endothelin-1 levels are high.

Flow-mediated dilation is reduced.

Tobacco smoke

Vasodilator function is impaired.

Endothelium-dependent vasodilation is reduced.

Nitric oxide availability is reduced.

Overstimulation of the sympathetic nervous system

Platelet aggregation has increased.

Physical exercise is being reduced.

Cardiovascular reactivity is altered.

Stiffening of the arteries

Vasoconstrictor-vasodilator equilibrium is disrupted.

Dietary errors

Obesity and being overweight

Antioxidant and anti-inflammatory activities are diminished.

Synthesis of nitric oxide is reduced.

Vitamin and mineral deficiencies

Hypertesion diagnosis

Ambulatory blood pressure monitoring (ABPM) is the most accurate technique to detect hypertension when a person has been examined and confirmed to have high blood pressure [99-101]. It is advised by guidelines to confirm increased blood pressure readings on a regular basis. Portable, automated cuffs are commonly used in ambulatory monitors, which measure blood pressure every 15–30 min during the day and every 15–60 min overnight [102]. Despite their diagnostic value, ambulatory monitors may be out of reach for many physicians and patients due to cost and time constraints and they can be inconvenient and disturb daily life and sleep [103, 104]. However, technological advancements have enabled the creation of new ‘cuffless BP monitoring devices that continually measure blood pressure without interfering with regular activities. Smartphone or wearable sensor technology can estimate blood pressure via ECG signals, photoplethysmogram (PPG) signals (using infrared light on the finger to determine skin blood flow), or a combination of both [105]. A wearable wristband to collect PPG data, a wearable heart rate belt to collect ECG signals, and a smartphone, for example, are all part of one system created. The signals from the wearable gadget communicate with the smartphone through Bluetooth to synchronise their measurements and transmit the wearer's blood pressure in real-time. Other devices have been created that calculate and record blood pressure measures using sensors in T-shirts [106], behind the ear [107], and in a computer mouse [108].

As with screening, the use of "smartphone apps" to assist in diagnosis is becoming more prevalent. According to a poll of ‘app users' in the United States, 31% of mobile phone owners used their phone to hunt for health information, with smartphone users accounting for the majority (52%) [109]. Despite the fact that this is a rapidly growing industry, with over 180 blood pressure apps already available, only 3.8 percent (7/184) of the blood pressure apps claimed any involvement of medical specialists in their development, and only a few apps have been rigorously tested [109]. Furthermore, the US Food and Drug Administration and the European Commission have yet to formally approve any mobile apps for use as measuring/diagnostic equipment. When one prominent mobile app was examined, the American Heart Association (AHA) found that there are too many inaccuracies with smart phone blood pressure apps [110], with mobile app-based blood pressure measures being wrong four out of five times [109, 110].

Inflammation and hypertension

Innate immune responses are quick and aren't exclusive to a single pathogen. They rely on phagocytic cells to recognise pathogen-associated molecular patterns (PAMPs) that are common to many pathogens but not found in the host or host-derived endogenous molecules that form as a result of cell death and injury [damage-associated molecule patterns (DAMPs) [111, 112]. These pathogen-associated compounds trigger inflammatory responses as well as neutrophil and macrophage phagocytosis. Both cell types have a variety of pattern recognition receptors on their cell surfaces (PRR). Toll-like receptors (TLRs), nucleotide-binding oligomerization domain receptors (NOD-like receptors), leucine-rich repeat (LRR)-containing proteins, retinoic acid-inducible gene (RIG)–like receptors (RLRs), and C-type lectin receptors (CLRs) recognise a variety of ligands, including lipopolysaccharide, peptidoglycans, [113-115]. The pro-inflammatory transcription factor nuclear-factor kappa–light-chain enhancer of activated B cells (NF-B) and the NACHT, LRR, and PYD domains-containing protein 3 (NLRP3) inflammasome are activated when TLRs are activated, resulting in the production of both signalling molecules such as prostaglandins and cytokines/chemokines. [115-117]. These cytokines attract neutrophils, monocytes, and dendritic cells, speeding up phagocytosis, acute-phase protein synthesis, and the adaptive immune system's transition to either the cell-mediated T-helper 1 (Th1) or humoral/antibody T-helper 2 (Th2) response. Although short-term inflammation is required for tissue defence, prolonged and excessive activation of the innate immune system causes harmful maladaptations and chronic inflammatory disorders like hypertension.


Monocytes are specialised circulating cells with chemokine receptors and PRRs that allow for the rapid recognition and phagocytosis of endogenous bacteria and host-derived compounds, resulting in the production of pro-inflammatory cytokines and the recruitment of immune cells [118]. Macrophages are phagocytic resident cells that remove apoptotic cells and release growth factors, resulting in tissue homeostasis. Macrophages also have a variety of PRRs that help with phagocytosis and can convey antigens to T cells by releasing cytokines and increasing inflammation [113]. The production of hypertension by intravenous injection of splenic cells from hypertensive deoxycorticosterone acetate (DOCA) salt-treated animals into normotensive rats provided evidence for the crucial function of macrophages in hypertension. Mononuclear infiltrates in the arterial and arteriolar walls, along with exudative thickening of the intima, caused luminal narrowing, resistance to peripheral blood flow, and hypertension, according to biopsies of recipients' kidneys and hearts. This suggests that activated innate immune cells are sufficient to cause hypertension [119].


Neutrophils are a type of myeloid cell that account for the majority of leukocytes in circulation. These innate immune cells are the initial line of defence against bacterial infection, but their significance in hypertension-related chronic inflammation is less clear [120]. Myeloperoxidase is one promising way by which neutrophils may mediate hypertension (MPO). Myeloperoxidase is a member of the heme peroxidase superfamily that is found mostly in neutrophils and monocytes. It produces reactive oxidants and radical species that are involved in lipid peroxidation. It's abundant in human atherosclerotic plaques, but it could also play a role in hypertension by acting as a nitric oxide catalytic sink [121]. In animal models, MPO-produced hypochlorous acid interacts with L-arginine to produce compounds that impair endothelial function by blocking NO production and acetylcholine-induced aortic relaxation [122]. Hypochlorous acid has also been shown to change high-density lipoprotein, causing endothelial nitric oxide synthase (NOS) to be displaced from its regular plasma membrane site, reducing its activity [123]. MPO and hypochlorous acid both lower the availability of NADPH, an important NOS cofactor [124]. These effects were shown in vivo in an MPO deletion mouse model, where mice were protected against toxemia-induced impairment of endothelial-dependent vascular relaxation [125], and in a pig model, where MPO injection resulted in reduced arterial blood flow [126]. These findings point to MPO's significance in hypertension regulation and its route as a potential therapeutic target in hypertension and cardiovascular disease.

Dendritic cells

Dendritic cells are cells that originate in the bone marrow and are found in the blood, lymphoid organs, and tissues. To activate T lymphocytes and control inflammatory responses, these professional antigen-presenting cells efficiently function as a bridge between the innate and adaptive immune systems [127]. Dendritic cells are classified in a variety of ways, but the most common are plasmacytoid dendritic cells and two types of conventional dendritic cells, while dendritic cells can also come from the monocyte lineage. Several mouse models have demonstrated the importance of dendritic cells in the development of Ang II–responsive hypertension, including transgenic mice lacking CD11-positive dendritic cells and mice lacking the Fms-like tyrosine kinase 3 ligand, which allows conventional dendritic cells to develop [128, 129]. AT1R appears to have an effect on dendritic cell differentiation. Dendritic cells with AT1R deletion produce less inflammatory cytokine and are less activated in response to lipopolysaccharide, implying a key link between dendritic cells and the renin-angiotensin system [130].

Dendritic cells impact T-cell activation to influence blood pressure through a variety of methods. T-cell activation necessitates not just antigen presentation to the T-cell receptor via a major histocompatibility complex, but also additional costimulatory interaction between the T cell and the dendritic cell. The interaction of B7 ligands (CD80 and CD86) on dendritic cells with CD27 on T cells is required for naive T-cell activation. Induced hypertension in mice by Ang II increases CD86 expression in dendritic cells. Blocking B7-dependent costimulation or deleting B7 ligands lowers Ang II–or DOCA salt-induced hypertension, and in fact, existing hypertension can be reversed with costimulation blocking [131]. Similarly, memory T-cell development requires costimulatory interaction between CD70 on dendritic cells and CD27 on T cells. In a mouse model of recurrent hypertensive stress, increased expression of dendritic cell CD70 leads to an accumulation of memory T cells in the kidney and bone marrow, which release interferon-gamma (IFN) and IL-17A, two cytokines linked to hypertension. Salt-sensitive hypertension develops in mice as a result of the buildup of bone marrow memory T cells and their extension to the kidney. The deletion of CD70 eliminates hypertension and memory T-cell responses [132]. Aldosterone activates dendritic cells in a similar way, resulting in an increase in IL-17-producing T cells that can be inhibited using mineralocorticoid receptor antagonists [133]. The ubiquitin-editing protein A20, on the other hand, appears to inhibit T-cell activation in dendritic cells. In mice, heterozygous deletion of A20 in CD11c-positive dendritic cells causes an exacerbated hypertensive response to low-dose Ang II infusion as well as an increase in TNF and IFN-secreting memory T cells in the kidney [134]. These data imply that dendritic cells play a critical role in the T-cell activation that causes hypertension.

T and B lymphocytes

T and B cells are key players in adaptive immunity, influencing and being impacted by the innate immune system. Antigen-presenting cells in the innate immune system (dendritic cells, macrophages, innate-like B cells, and others) customise T cell development and adaptive responses to antigens [135]. Lymphocytes also share innate immunity properties such antigen and cytokine detection in both B and T cells, as well as the presence of several TLR on T lymphocytes [136]. Several studies demonstrating the function of adaptive immunity in the development of hypertension will be discussed in this section.

T lymphocytes

T cells mature in the thymus and then travel to lymphoid organs like the spleen and lymph nodes, where they remain inactive until they are activated by an antigen-presenting cell. T cells have been linked to hypertension through a variety of processes, including the generation and activation of cytokines, as well as infiltration of the renal vasculature and the central nervous system. The thymus is an important organ for T cell growth and education. Early research in athymic mice revealed that lymphocyte depletion results in the prevention or correction of hypertension in a variety of mouse models [137-140]. Salt-induced hypertension is resistant in athymic DOCA-treated mice, but thymus transplantation restores salt sensitivity [141]. The immunosuppressant cyclophosphamide reduces the hypertensive response of Sprague-Dawley rats after a partial renal infarction. The Lyon strain of genetically hypertensive rats showed similar results [141, 142]. Furthermore, transferring lymph node cells from rats with renal infarction or splenocytes from DOCA salt-treated rats to normal rats raises blood pressure in the recipient, implying that the development of hypertension requires an intact T-cell immune system [119, 143].

B lymphocytes

B lymphocytes, with their ability to recognise and process antigens as well as make antibodies, are essential for adaptive immunity. Several investigations have found that severely hypertensive people have high levels of IgG, IgM, and IgA antibodies [144, 145]. Ang II infusion increases the amount of splenic B cells and circulating IgGs in mice, as well as causing significant IgG buildup in the aortic adventitia. Furthermore, depletion/regulation of B-cell activity via immunological modulation (e. g., rituximab) or knockout models such as B-cell activating factor receptor knockout (BAFF-R/) mice has been demonstrated to reduce mean arterial pressure and the hypertensive response to Ang II in several investigations [146, 147]. In a mouse model of SLE mice, alternative medicines such as bortezomib, a proteasome inhibitor that reduces plasma cell antibody production, have showed promise in reducing bone marrow plasma cells. Bortezomib treatment reduced renal injury/glomerulosclerosis, B and T lymphocyte infiltration into the kidney, and mean arterial pressure in mice [147]. These findings are in contrast to recent research that suggests that adoptive transfer of T cells but not B cells restores Ang II–induced hypertension in RAG-1/mice [146]. This apparent contradiction, however, could indicate that B-cell activation necessitates contact with T cells, and the two types of cells may have separate methods for causing hypertension.


Hypertension has been identified as a significant risk factor for the development of a variety of cardiovascular illnesses. There is clear evidence that lifestyle factors may alter blood pressure values based on current literature data. Then, in hypertension individuals, lifestyle adjustments can have a beneficial effect, lowering global cardiovascular risk and all-cause death.

The role of immunity as a common thread underpinning multiple organ systems' hypertension processes. Exploring the genetic and environmental variables that predispose these cells to react to common stimuli, as well as gaining a better knowledge of how immune cells communicate with target organs to induce hypertension, can help us create new treatments for this prevalent disease.




All the authors have contributed equally.


Declared none


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