Renal and Extrerenal Effects of Sodium Retention
The renal pathway of pathogenesis is inextricably linked to changes in blood volume. Excess aldosterone acts on the renal tubules, stimulating the reabsorption of $Na^+$ ions. This inevitably causes plasma hyperosmolality—an increase in the osmotic pressure of the blood. The hypothalamic-pituitary system responds to hyperosmolality by activating the synthesis and secretion of antidiuretic hormone (ADH, vasopressin). ADH binds to its receptors and enhances the reabsorption of excess fluid from the primary urine in the distal renal tubules. The result of this cascade is an increase in extracellular fluid volume and the development of marked hypervolemia (increased circulating blood volume).
The extrarenal pathway is caused by changes in the properties of the vascular wall and myocardium due to electrolyte imbalance. Aldosterone promotes the active transport of excess $Na^+$ into the cells of various tissues. Intracellular sodium accumulation triggers several severe consequences:
- Cellular swelling: Hydration of the endothelium and myocytes of the vascular walls occurs, which physically narrows their lumen.
- Increased myocyte tone: The basal tone of the smooth muscle in the vascular wall and heart increases.
- Sensitization (increased sensitivity): The vascular walls and myocardium become abnormally sensitive to pressor (hypertensive) agents, such as catecholamines and angiotensin II.
Hemodynamic Features in Endocrine Disorders
With an excess of thyroid hormones (hyperthyroidism), heart rate (HR), stroke volume, and cardiac output increase significantly. This condition is characterized predominantly by isolated systolic arterial hypertension, while diastolic pressure remains low or normal. Notably, if elevated diastolic BP is recorded against the background of hyperthyroidism, it usually indicates concomitant pathology (another secondary hypertension or essential hypertension).
In cases where the pathology is accompanied by dystrophic changes in the arterial walls, high diastolic BP develops. The main mechanism here is associated with a sharp increase in total peripheral resistance (TPR). Notably, heart rate and cardiac output in this hemodynamic variant are generally reduced.
Imbalance of Vasoactive Metabolites
The pathogenesis of many types of hypertension is based on an imbalance of vasoactive substances. Blood pressure levels depend on the equilibrium between vasoconstrictor and vasodilator metabolites.
1. Metabolites with significant hypertensive (pressor) action:
- Angiotensins (angiotensin II plays the most prominent role).
- Biogenic amines (serotonin, tyramine, and catecholamines).
- Endothelins (potent vasoconstrictors of endothelial origin).
- Thromboxane $A_2$ (an arachidonic acid metabolite acting as an aggregator and vasoconstrictor).
- Prostaglandins of the F group (e.g., $PGF_{2\alpha}$).
- Cyclic nucleotides (hypertensive forms, mainly cAMP under certain conditions or against a background of decreased cGMP).
2. Metabolites with marked hypotensive (depressor) effect:
- Kinin system peptides (especially bradykinin and kallidin).
- Prostaglandins of the E and I groups (e.g., prostacyclin).
- Nitric oxide (NO)—a crucial endothelial relaxation factor.
- Natriuretic factors (including atrial natriuretic peptide).
- Acetylcholine and adenosine.
- Gamma-aminobutyric acid (GABA).
Role of Hypoxia in the Development of Hypertension
Tissue oxygen deprivation (hypoxia) acts as a potent trigger for vascular disorders. It triggers three parallel pathogenetic processes that together lead to a sustained increase in blood pressure:
- Pressor factor imbalance: Hyperproduction and/or excessive activation of metabolites with hypertensive action occurs.
- Depressor factor imbalance: Hypoproduction (decreased formation) and/or accelerated inactivation of metabolites with hypotensive action is observed.
- Receptor abnormalities: The sensitivity of the cardiac and vascular receptor apparatus to metabolites with hyper- or hypotensive effects changes.