Leptin and hypertonia

Obesity in combination with hypertension provokes a higher mortality rate. It happens due to damage not only to the heart and blood vessels, but also to the involvement of the kidneys in the pathological process. The connection of these diseases can be traced in irrational nutrition, unbalanced metabolism (insulin resistance), impaired vascular permeability, pathologically altered neuroedocrine background, functional imbalance of the kidneys, perverse immune response, and inflammatory response.

Recently, more and more new data have appeared on the interest in the combined pathology of the intestinal microbiota, uric acid, incretin, which stimulates the synthesis of insulin. The article presents an attempt to give a generalized assessment of the mechanism of development of hypertonia against the background of obesity.


  1. The connection between obesity and hypertonia.
  2. Provocative factors.
  3. The pathogenesis of hypertonia in obesity.
  4. Final results.

The connection between obesity and hypertonia

The transformation of normal blood pressure into hypertonia has many causes: genetics, behavioral habits, nutrition, environment.

The combination of obesity and hypertonia is always pregnant with two important consequences:

  1. First, patients have an increased risk of sudden death from cardiovascular problems, cerebrovascular accident,  and chronic kidney disease.
  2. Secondly, the risk of resistance to drugs of the antihypertensive group is growing, which requires either an increase in the number of drugs or the use of the most complex techniques like sympathetic denervation of the renal arteries.

In addition, it is obvious that hypertensive patients themselves are more inclined to gain extra pounds than normotensive patients. So, we may say that hypertonia itself is the cause of obesity. All this suggests a close pathophysiological relationship between these two pathologies.

Provocative factors

Not so long ago, the leading role in the development of obesity was attributed to supercaloric nutrition with fats, fast carbohydrates, excess sodium, and physical inactivity. There were facts to support these ideas. For example, the introduction of high-fructose corn syrup into the American diet has caused an increase in obesity, diabetes, and heart problems.

Indeed, fructose corn syrup has colossal atherogenic properties and increases the level of triglycerides, insulin, cholesterol in the bloodstream. It leads to the development of metabolic syndrome, a high risk of heart attacks, and cerebrovascular accidents. In addition, this syrup stimulates the growth of uric acid in the blood and adipose tissue in the liver.

However, the suggestion that fructose and uric acid are triggers of hypertonia is debatable. It has not been experimentally proven that the rejection of fructose leads to at least some reduction in arterial hypertension. Only the minimization of sodium in food significantly reduces blood pressure figures. This means that only a combination of fructose with other dangerous components of the diet (sodium, fatty foods) can provoke negative consequences.

Natural cardioprotectors

Deficiency of omega-3 polyunsaturated fatty acids negatively affects the heart muscle and vascular endothelium. It can be provoked by the prevalence of vegetable oils and red meat in the menu, which contains a lot of omega-6.  But eating fish oil, seafood and marine fish minimizes blood pressure. These products are filled with omega-3.

A balanced diet based on leafy salads and vegetables provides the body with the necessary amount of inorganic nitrogen. It increases the bioavailability of nitric oxide, a very powerful vasodilator that ensures the normal functioning of the vessel wall. Such nutrition based on natural cardioprotectors is useful for hypertensive patients and anyone who suffers from obesity.

Intestinal microbiota

Today, everyone understands that the microbiota is the totality of all microorganisms that inhabit the human intestine and are crucial for immunological, hormonal, and metabolic homeostasis. Changes in the quality or quantity of the microbiota, which are associated with genetics, can lead to metabolic disorders up to obesity, diabetes, insulin resistance, and hypertonia themselves. Nothing else is required. But both the quality and quantity of the microbiota can change the diet. The consequences of such changes are considered a dysimmunity, the development of inflammation. That is why pre- and probiotics are used in the treatment of obesity and hypertonia against its background.

The pathogenesis of hypertonia in obesity

There are many provoking moments in order for obesity to develop hypertonia: nutrition, genetics, ecology. Let’s get to know them better.

Vascular damage

Vascular loss of elasticity is the earliest sign of endothelial damage in obesity, which precedes the development of hypertonia. Rigidity of capillaries can often be found in normotonic patients who are overweight and are in the stage of prehypertonia. Its development is provoked by a violation of the connective tissue matrix and the structure of smooth muscles in the vessel wall. Endothelial dysfunction, provoked by insulin resistance, also contributes to this process.

In addition, insulin resistance in obesity can be triggered by impaired synthesis of lipids and bioactive substances:

  • angiotensinogen;
  • aldosterone-stimulating factor;
  • dipeptidyl peptidase type 4 (DPP-4);
  • leptin;
  • resistin;
  • adiponectin;
  • tumor necrosis factor;
  • interleukin-6.

Upon closer examination, it turns out that these are the same substances that stimulate the development of hypertonia in obesity.

Kidney dysfunction

Obesity is accompanied by increased sodium reabsorption in the distal tubules of the nephron. Blood pressure automatically rises In response to this. In addition, the same effect is possible with an increase in the amount of fat and its growth in the form of an extracellular matrix, with compression of the renal medulla.

Hyperinsulinemia, activation of the sympathetic nervous system, and the renin-angiotensin complex also increase sodium reabsorption. At the same time, blood pressure rises and kidney vessels are remodeled with the development of chronic inflammation, impaired function of the vessel wall, and proliferation of smooth muscles. A systemic immune response occurs as a result, the concentration of uric acid increases, tubulointerstitial inflammation, oxidative stress and fibrosis increase. All together leads to injury to the renal tissue.

Hyperactivation of the sympathetic nervous system

A set of extra pounds is associated with the activation of sympathetic nerve fibers in various organs and tissues, including the heart and blood vessels, kidneys, and skeletal muscles. An increase in norepinephrine is recorded in the kidneys depending on the severity of hypertonia. This indicates the activation of the sympathetic nervous system. Excessive activity of the heart is observed only in patients with obesity and hypertonia,

Factors that provoke hyperactivity in obesity include:

  • hyperleptinemia;
  • increased level of apelin;
  • the absence of a nocturnal decrease in blood pressure against the background of insulin resistance, inflammation or dysfunction of the autonomic nervous system;
  • sleep apnea (OSA).

Angiotensin activation

Cross-contact of angiotensin II and aldosterone correlates vasoconstriction independently of renal control. The main mechanism is inactivation of the insulin metabolic pathway with simultaneous activation of kinase enzymes and limited impairment of capillary function. Pathological changes in fat cells in obese patients provoke vascular resistance to insulin and systemic insulin resistance.

This disrupts the sympathetic nervous system and angiotensin. Structural changes in the kidneys also play a role in the development of hypertension in obesity. Local stimulation of fatty layers and the synthesis of angiotensin by fat cells indicates dysfunction of adipose tissue. At the same time, a high-fat diet stops hypertonia.

Excess aldosterone in obesity provokes lipid peroxidation, reduces the bioavailability of nitric oxide, causing insulin resistance. Aldosterone receptor antagonists can improve vascular function and attenuate the damaging effects of angiotensin II, i.e. lower blood pressure.

Immunity and inflammation

Infiltration of lipid layers by macrophages also contributes to the development of insulin resistance and impairs endothelial function. Some macrophages provoke inflammation, while others cause a protective effect. Adaptive immunity is also involved in the development of hypertonia. Helper cells control pro-inflammation, oxidative stress, and macrophage vascular infiltration.

Uric acid

High plasma uric acid levels damage the kidneys and the cardiovascular system. This condition is caused by impaired function of fat cells, immune and inflammatory responses, angiotensin hyperactivation, oxidative stress, and a hyperfructose diet.

Mechanisms of damaging action of uric acid:

  • pro-inflammation;
  • innate immune response;
  • activation of angiotensin in the vesel wall;
  • renal ischemia.

An increase in the concentration of uric acid is associated with the absence of a decrease in blood pressure at night. There is evidence that normalization of uric acid, for example, with allopurinol, can lower daily diastolic and daytime systolic blood pressure.


Epigenetic mechanisms are DNA methylation and RNA regulation. It is possible that the action of epigenetic factors in the prenatal period controls the risk of developing metabolic disorders in the fetus and in early childhood.


Hormones of the gastrointestinal tract (incretins) play an important role in the immune response, which occurs as a reaction of tissue sensitivity to insulin. Incretins are associated with leptin. They have a vasodilating effect with a help of angiotensin and are able to restore the level of natriuretic factor, which is reduced in patients with obesity.


Estrogens are protectors in their essence, reducing the risk of pathologies of the heart and blood vessels, increasing the sensitivity of tissues to insulin. Normally, estradiol activates the synthesis of ACE. The opposite occurs with obesity and excessive salt intake. This is an increase in the expression of angiotensin. There may be a crossover between estrogen and mineralocorticoid receptors, which is regarded as a violation of the immune and inflammatory responses with the formation of rigidity of the vessel wall.

Final results

Thus, hypertonia associated with obesity develops under the influence of many provocateurs.

The main ones among them are:

  • insulin resistance;
  • violation of the synthesis of adipokines;
  • hyperactivation of sympathetic fibers and angiotensin;
  • structural and functional disorders of the kidneys, heart, blood vessels;
  • dysimmunity;
  • changes in the intestinal microbiota;
  • hyperuricemia;
  • minimization of estrogen function.

Changing the lifestyle, minimizing the calorie content of the diet and dosed physical activity can correct the situation.

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