This document discusses the hormonal regulation of blood pressure. It describes how the renin-angiotensin-aldosterone system (RAAS) responds to low blood pressure by increasing renin, angiotensin II, and aldosterone levels to stimulate sodium retention and raise blood pressure. For high blood pressure, atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) act to reduce blood pressure by increasing sodium excretion. The document also outlines treatments for hypertension including ACE inhibitors, angiotensin II receptor blockers, beta blockers, and aliskiren which targets the RAAS pathway.
3. INTRODUCTION
• Blood pressure is the force produced by circulating blood upon the walls of the
blood vessels.
• It is normally expressed in terms of the systolic pressure over the diastolic
pressure and it is measured in millimetres of mercury (mmHg).
• It is measured using a sphygmomanometer.
• It is regulated by controlling 3 factors: cardiac output, total peripheral resistance
and blood volume.
• Physiological variation in blood pressure can be due to different factors such as
temperature, emotional stress, physical activity, changes in posture, and it also
varies across age and gender.
4. Cont.…
• Blood pressure can be classified into different categories
Category
Systolic BP,
mmHg
Diastolic BP,
mmHg
Optimal < 120 < 80
Normal 120–129 80–84
Prehypertension 130–139 85–89
Grade 1 hypertension 140–159 90–99
Grade 2 hypertension 160–179 100–109
Grade 3 hypertension ≥ 180 ≥ 110
6. Hypotension (Low Blood Pressure)
• A condition where the systemic blood pressure is below accepted low values.
• There is no accepted standard hypotensive value however, pressures below
90/60 are recognized as hypotensive.
Symptoms
• The most common symptoms include blurred or fading vision, dizziness and
fatigue.
Causes
• Blood loss, pregnancy, heart failure, dehydration and severe allergic reaction.
7. Response to Hypotension
Renin–Angiotensin–Aldosterone System (RAAS)
• A system of hormones, proteins and enzymes
• It regulates blood pressure and fluid balance
• It is the main hormonal pathway through which blood pressure is
increased.
• It is activated by low Na+ level, arterial blood pressure and blood volume.
• It is composed of renin, angiotensin and aldosterone.
8. Cont …
• Renin was first discovered by physiology researchers Robert Tigerstedt and Per Bergman
from the Karolinska Institute, Stockholm in 1898.
• In 1934, Godblatt found that renin secretion and blood pressure increased following renal
artery constriction.
• Six years after Godblatt’s discovery, Page, Helmer as well as Braun-Menendez, discovered
angiotensin.
Robert Tigerstedt
9. Important Components of the RAAS
Renin
• A single-chain polypeptide of 340 amino
acids with molecular weight of ~37 kDa.
• Produced by Juxtaglomerular cells.
• Hydrolyses angiotensinogen into
angiotensin I.
Renin
Nephron
10. Cont...
Angiotensinogen (AGT)
• A 485 amino-acid, 60KDa protein primarily synthesized by hepatocytes.
• It is synthesized as an inactive precursor for angiotensin.
• Its activation involves a cleavage of the N-terminal by renin to form angiotensin I.
N- terminal tail sequence of angiotensinogen indicating the renin and ACE cleavage sites, the glycosylation
site, and the site where a disulfide bond is formed.
11. Cont…
Angiotensin I (AT I)
• It is made of 10 amino acids, with a molecular weight of ≈1.3 kDa.
• It is produced by cleavage of angiotensinogen
by renin.
• It is a relatively inactive hormone.
• It acts as a precursor of angiotensin II, a more
potent hormone.
12. Cont…
Angiotensin II (AT II)
• It is a hormone formed by the action ACE on
angiotensin I.
• It is an eight amino acid hormone.
Main physiological functions of AT II
1. It enhances reabsorption of Na, Cl, and water in the
proximal convoluted tubule.
2. It stimulates the adrenal cortex to release aldosterone.
3. It stimulates the secretion of ADH from the posterior pituitary gland.
13. Cont…
Aldosterone
• It is a steroid hormone synthesized
by the zona glomerulosa of the
adrenal cortex.
Functions
• It stimulates the principal cells in the collecting
duct to reabsorb more Na+ and Cl- and secrete more K+.
Aldosterone
16. Mechanism of Action of Aldosterone
• d
ENaC-epithelial Na+ channel; Hsp-heat shock protein; MR-mineralocorticoid receptor; GR-glucocorticoid receptor; SRE-steroid
response element; 11β-HSD2, 11-β-hydroxysteroid dehydrogenase type 2, Sgk- serum and glucocorticoid-regulated kinase, Ki-
RasA- Kirsten rat sarcoma A.
17. Antidiuretic Hormone (ADH)
• It is nonapeptide derived from the preprohormone called prepropressophysin.
• It is synthesized by supraoptic nucleus of the hypothalamus and transported to the
pituitary gland by neurophysins for storage.
Function(s)
• It enhances water reabsorption in the last part of the DCT and the collecting duct.
18. Cont…
Mechanism of Action of ADH
PKA-protein kinase A, cAMP-cyclic adenosine monophosphate, V2R-vasopressin receptor 2, ATP- Adenosine triphosphate, AQP2-
aquaporin 2, AVP-arginine vasopressin.
19. Epinephrine and Norepinephrine
• They are secreted due to stimulation by the sympathetic system on the adrenal medulla.
• Norepinephrine is also called noradrenaline and it binds to the α-adrenergic receptors on the
arteriolar smooth muscles.
• Epinephrine is also called adrenaline and it binds to both the β2-adrenergic receptors on the
heart and the α-adrenergic receptors on the arteriolar smooth muscles.
Norepinephrine Epinephrine
20. Cont...
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Binding to α1 receptors promotes production of IP3 which stimulates increase in intracellular Ca2+ leading to smooth
muscle contraction. Binding to α2 receptors on the other hand, promotes a decrease in cAMP-cyclic adenosine
monophosphate levels, resulting in smooth muscle contraction. Binding to β receptors leads an increase
in intracellular cAMP levels , resulting in heart muscle contraction and smooth muscle relaxation.
21. Hypertension (High Blood Pressure)
• It is a clinical condition where blood pressure is higher than normal.
• Secondary hypertension is the one that occurs secondary to another known
primary problem.
Examples:
• Renal hypertension is due to problems and malfunctions of the kidney that result
in unnecessary triggering of the RAAS. For example, compression of the vessel by
a tumour.
• Endocrine hypertension is due to excessive secretion of epinephrine and/or
norepinephrine. For example; Due to a pheochromocytoma.
• Primary hypertension is due to a variety of unknown causes rather than by a
single disease entity.
• Hormonal regulation of hypertension is by the Atrial Natriuretic Peptide (ANP)
and Brain Natriuretic Peptide (BNP).
22. Cont.…
• Adolfo De Bold at. al. discovered the natriuretic factor in 1981, which lead to the
isolation and discovery of atrial natriuretic peptide (ANP).
Adolfo De Bold
23. Response to High Blood Pressure
Atrial Natriuretic Peptide (ANP) and Brain Natriuretic Peptide(BNP)
• They are both produced by cardiomyocytes.
• They are stored in granules and released when the heart muscle cells are mechanically
stretched by an expansion of the circulating plasma volume.
ANP
BNP
26. DRUGS THAT TREAT HYPERTENSION
Captopril (ACE inhibitor)
Losartan- the first ARB
Aliskiren- RAAS inhibitor Carvedilol- β-adrenergic
receptor blocker
Atenolol- β-adrenergic receptor
blocker
27. Summary
• Blood pressure is the force exerted by blood on the walls of the blood vessels.
• The normal blood pressure is 120 mm Hg systolic pressure and 80mm Hg diastolic
pressure.
• Blood pressure is regulated by two mechanisms; the short-term control and the
long-term control.
• The long-term control of blood pressure involves regulation by different
hormonal systems.
• The main hormonal system that increases blood pressure is the RAA system
whereas the main hormone that decreases blood pressure is atrial natriuretic
hormone.
• Hypertension can also be treated by administration of ACE inhibitors and
angiotensin II receptor blockers.
Pheochromocytoma is a tumor that grows from chromaffin cells in the adrenal glands.
Renal artery stenosis, or the narrowing of one or both of the arteries that carry blood to the kidneys, decreases kidney blood flow. This drop in blood flow stimulates renin production
Reninomas are rare tumors of the kidney cells that make renin (juxtaglomerular cell tumors). They produce excessive amounts of renin, resulting in severe hypertension, high aldosterone levels, and low blood potassium levels
