Vasopressin (ADH) and vascular tone control
Antidiuretic hormone (ADH, vasopressin) plays a crucial role in maintaining blood pressure. One of the pathways for its effects involves acting on vascular smooth muscle via specific $V_1$ receptors.
Mechanism of action via $V_1$ receptors:
- The hormone binds to $V_1$ receptors located on the membranes of vascular smooth muscle cells.
- The resulting complex activates the enzyme phospholipase C.
- An intracellular cascade is triggered, leading to the release of $Ca^{2+}$ ions from the endoplasmic reticulum.
- An increase in intracellular calcium concentration causes contraction of the smooth muscle layer, leading to vasoconstriction.
Pathology: Diabetes insipidus Impairment of the ADH system leads to the development of diabetes insipidus. Etiologically, it is divided into two types:
- Central (hormone deficiency due to posterior pituitary dysfunction).
- Nephrogenic (impaired hormonal signal transduction at the level of renal receptors).
The key clinical manifestation of the disease is polyuria, i.e., the pathological excretion of very large volumes of urine with a characteristically low specific gravity.
Aldosterone and sodium retention
Aldosterone is the most active hormone in the mineralocorticoid group. Its main task is the retention of $NaCl$ in the body, which directly affects blood volume.
Synthesis and stimulation: The hormone is synthesized in the cells of the zona glomerulosa of the adrenal cortex, with cholesterol serving as its precursor. Aldosterone secretion increases sharply during:
- a decrease in blood $Na^+$ ion concentration;
- an increase in $K^+$ ion concentration;
- activation of the renin-angiotensin system (RAS).
Hypersecretion of this hormone by the adrenal cortex leads to a condition known as hyperaldosteronism.
Molecular mechanism of action: Upon reaching the kidneys via the bloodstream, aldosterone penetrates the cells of the renal tubules. There, it binds to its specific receptor (which may be located in the cytoplasm or nucleus). This hormone-receptor complex induces the synthesis of new functional proteins.
Role of induced proteins:
- They form channels that ensure the reabsorption of $Na^+$ ions.
- They create conditions for the excretion of $K^+$ ions.
- They increase the number of membrane pumps — $Na^+, K^+$-ATPase.
- Some of the synthesized proteins serve as enzymes of the tricarboxylic acid (TCA) cycle. This is necessary for enhanced ATP generation, since active ion transport requires high energy expenditure.
Atrial natriuretic peptide (ANP)
While the RAAS (the main regulator of water-electrolyte balance) strives to increase pressure and retain fluid, Atrial Natriuretic Peptide (ANP) acts as its direct physiological antagonist, specifically acting as an antagonist to angiotensin II.
Characteristics and secretion: ANP is a peptide hormone. It is synthesized and stored as an inactive prohormone directly in cardiomyocytes. The primary stimulus for its release into the blood is mechanical stretch of the atria, which occurs when blood volume increases and blood pressure rises.
Mechanism of action: The hormone acts on target cells in the kidneys, adrenal glands, and peripheral arteries. The ANP receptor located on the plasma membrane of cells is unique in that it is catalytic in itself — it possesses guanylyl cyclase activity. Upon binding with ANP, the receptor catalyzes the formation of the second messenger cyclic guanosine monophosphate (cGMP) from GTP.
Main physiological effects of ANP:
- Direct inhibition of renin and aldosterone production and secretion.
- A sharp increase in the excretion of $Na^+$ ions and water in the urine.
- A vasodilatory effect and, consequently, a decrease in blood pressure.
Briefly: answers to topical questions
What is the mechanism of action of vasopressin via $V_2$ receptors?
The mechanism of action of vasopressin (ADH) via $V_2$ receptors is based on the activation of the adenylate cyclase system.
- Binding — ADH binds to the $V_2$ membrane receptor on the basolateral membrane of cells in the collecting ducts and distal tubules of the kidneys.
- Adenylate cyclase activation — the hormone-receptor complex activates the enzyme adenylate cyclase, which catalyzes the formation of cAMP from ATP.
- Protein kinase A activation — cAMP converts protein kinase A into its active form.
- Phosphorylation — the active kinase phosphorylates regulatory proteins (transcription factors).
- Gene expression — transcription of the aquaporin-2 gene is induced.
- Physiological effect — aquaporin-2 is integrated into the apical membrane, ensuring an increase in facultative water reabsorption.
Which intermediate enzymes are involved in the synthesis of aldosterone from cholesterol?
The literature indicates the following enzymes and stages for the synthesis of aldosterone from cholesterol:
- 20,22-desmolase (P450scc / CYP11A1) — the cholesterol side-chain cleavage enzyme; the first stage of corticosteroid biosynthesis: cholesterol is converted into pregnenolone.
- 21-hydroxylase (P450c21 / CYP21A2) — in aldosterone synthesis, progesterone hydroxylation is initially carried out by 21-hydroxylase.
- $11\beta$-hydroxylase (P450c11$\beta$ / CYP11B1) — this is followed by the action of 11-hydroxylase.
- Aldosterone synthase (P450c11AS / CYP11B2) — indicated in the literature as an enzyme of steroidogenesis.
ANP is an emergency pressure "relief valve." Remember the logic: high pressure stretches the atria (heart) $\rightarrow$ the heart releases ANP $\rightarrow$ ANP forces the kidneys to "dump" sodium (natriuresis) and water. Less water means lower pressure.
Class and exam questions
What stimulates the production of atrial natriuretic peptide?
The primary stimulus for ANP secretion is stretching of the atrial walls, which occurs with elevated blood pressure and increased circulating blood volume.
What is the specific feature of the ANP receptor?
The ANP receptor is catalytic. It has built-in guanylyl cyclase enzyme activity and, upon activation, directly converts GTP into cGMP.
What urinalysis changes are typical for diabetes insipidus?
Pronounced polyuria develops — the excretion of an inappropriately large amount of urine. At the same time, urine specific gravity is pathologically decreased due to the kidneys' inability to concentrate urine under conditions of ADH deficiency or resistance.
What else to study on this topic
- Interaction of angiotensin II and atrial natriuretic peptide
- The role of phospholipase C in the mechanism of action of ADH
- Pathogenesis of nephrogenic diabetes insipidus
- Stages of aldosterone biosynthesis from cholesterol
- Feedback mechanisms in the renin-angiotensin-aldosterone system
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