vascular physiology Flashcards
systolic blood pressure
-The pressure in the arteries when the heart contracts (beats) and pumps blood out into the body.
-normal young adults= 120 systolic
diastolic blood pressure in the system
-The pressure in the arteries when the heart is at rest between beats and refills with blood.
-normal adult around 70mm Hg
-both rises slowly with age
natural changes in blood pressure
-blood pressure is the highest in the aorta as the vessel is close to the heart
-Blood pressure decreases significantly as blood moves into smaller arteries and arterioles. This is because: The vessels become smaller in diameter, increasing resistance to flow
-By the time blood reaches the capillaries, pressure is much lower and relatively steady (no longer pulsatile). This low pressure is crucial for:
Allowing time for exchange of oxygen, nutrients, and waste between blood and tissues
-pressure continues to drop in the veins and venules
hypertension(high blood pressure)
-Blood pressure greater or equal140 (systolic)/ 90 (diastolic) mm Hg
or
-a rise in blood pressure greater or equal 30 (systolic)/ 15 (diastolic) mm Hg
on at least 2 occasions at least 4 hours apart
- increased risk of other diseases e.g., heart attacks
primary (essential HT)
-no apparent cause (90 - 95% of cases,) Associated risk factors - genetic predisposition, obesity, alcohol
consumption, lack of exercise, smoking
secondary HT
- 5-10% of cases - kidney disease or endocrine disease e.g. tumor of adrenal - secretes excessive adrenaline
major mechanisms that regulates blood pressure
-there are many but theses are the important ones:
-volume of blood pumped into the arterial tree. kidney functions relates to this.
-stiffness of the arteries(vascular tone) : Vascular smooth muscle
contractile tone Endothelial cell function
poiseuilles law
The radius of a blood vessel presents the largest
contribution to resistance of blood flow, since resistance
is inversely proportional to the radius to the fourth power
(resistance 1/∝ r4).
-essentially the narrower you arteries the harder it is to push blood through=higher resistance
structure and function of the nephron
-Kidneys receive approximately 25 % of the cardiac output, and filter approximately 15 times the extracellular fluid volume per day
regulation of the blood volume via diuretics
-Early Distal Tubule Diuretics (e.g., Bendroflumethiazide):
These act on a part of the kidney called the distal convoluted tubule.
They block a “salt transporter” (Na+/Cl-) that normally reabsorbs salt into your body.
Result: Less salt is reabsorbed, so more water is lost in urine.
Potassium-Sparing Diuretics (e.g., Amiloride):
These also work in the distal tubule, but they block a different transporter (Na+/K+ exchanger).
They let the body get rid of salt and water but keep potassium, which is important for your heart and muscles.
Loop Diuretics (e.g., Furosemide):
These act on the Loop of Henle, a different part of the kidney.
They block another salt transporter (Na+/K+/2Cl-) that reabsorbs a lot of salt.
Result: A large amount of water and salt is lost, making them very powerful diuretics.
effects of ageing on blood pressure
-premenopausal women have a lower blood pressure than men
-post penapausaal women have a higher blood pressure than men
- this is because oestrogen
how does the blood pressure cuff work
-Inflation: The cuff is inflated to a pressure higher than the expected systolic pressure. This temporarily stops blood flow in the artery.
Deflation: The cuff is gradually deflated, and blood starts to flow through the artery again.
A stethoscope or a sensor detects the sound or pulse of blood flow as the pressure decreases.
Measuring Systolic Pressure
The first sound detected (called the Korotkoff sound) occurs when the blood starts to flow again as the cuff pressure equals the systolic pressure. This is recorded as the top number in a blood pressure reading.
Measuring Diastolic Pressure
The last sound heard (when the blood flows freely without turbulence) corresponds to the diastolic pressure. This is recorded as the bottom number in the reading
how does Oestrogen increase NO signaling
Oestrogen Binds to Receptors:
Oestrogen binds to ERα or ERβ (classic receptors) or GPER (a rapid-response receptor) in the cells lining the blood vessels (endothelial cells).
Activation of eNOS:
These receptors stimulate an enzyme called endothelial nitric oxide synthase (eNOS), which is responsible for making NO from a molecule called L-arginine.
Increased NO Release:
As eNOS becomes more active, more NO is produced and released into the blood vessels.
Effects of Oestrogen signalling on prostaglandins synthesis
-Vasodilation: NO helps relax the smooth muscle in the blood vessel walls, leading to wider vessels and better blood flow.
Reduced Inflammation: NO reduces inflammation in blood vessel walls, protecting against damage.
Anti-Clotting: NO prevents platelets (cells that help blood clot) from sticking to the vessel walls, reducing the risk of clots.
blood vessels overviews
-Blood vessels have 3 layers; connective tissue adventitia, smooth muscle
layer and endothelium.
Aorta and large arteries contain a large amount of elastic tissue
(to respond to stretching of vessel with heart beat)
Arterioles less elastic tissue much more smooth
muscle – major site of resistance to flow
Capillaries made from endothelial cells (single cell thick)
Veins and venules – walls are only slightly thicker than
capillaries, they contain relatively little smooth muscle
blood flow in the veins
- assure single direction movement
-movement back to the heart may be facilitated by my muscular movements.
capillary bed
-Capillaries - oxygen and
nutrients enter the interstitial fluid and carbon dioxide and waste products enter the
bloodstream – transit time
from arteriolar to venule
end of an average sized
capillary is 1-2 seconds.
-When dilated diameter of capillaries
is just sufficient to permit RBCs to
squeeze through in single file
transport across capillary beds
-filtration: fluid exits capillary as the capillary hydrostatic pressure is greater than blood colloidal osmotic pressure
-no net movement: since capillary hydrostatic pressre= blood colloidal osmotic pressure
-reabsorption: fluid re-enters capillary since capillary hydrostatic pressure is less than blood colloidal osmotic pressure
baroreceptors
-pressure sensors= activates when the blood vessels strech.
-detect blood pressure
-When blood pressure increases, the walls of these vessels stretch more, activating the baroreceptors.
When blood pressure decreases, the stretch is less, and the baroreceptor activity decreases.
-found in the carotid sinus and carotid nerve
Mechanism of baroreceptors
Pathway:
Signals travel to the medulla oblongata.
Inhibitory Interneurons:
Activated by baroreceptor input in the brainstem. Modulate sympathetic nervous system (SNS) activity.
Reciprocal Sympathetic Changes:increased baroreceptor activity (high blood pressure):
Activates inhibitory neurons → Decreases SNS activity → Lowers blood pressure.
Decreased baroreceptor activity (low blood pressure):
Reduces inhibitory neurons → Increases SNS activity → Raises blood pressure.
Sympathetic Nervous System Pathway:
Pre-ganglionic neurons release acetylcholine (ACh) onto nicotinic receptors in the sympathetic ganglion.
Post-ganglionic neurons release noradrenaline (NA) onto targets (e.g., arteries).
Effects on Target Organs:
Increased SNS activity:
Heart: Increases heart rate and contractility → Raises cardiac output.
Vessels: Causes vasoconstriction → Increases blood pressure.
Decreased SNS activity:
Heart: Lowers heart rate and contractility → Reduces cardiac output.
Vessels: Causes vasodilation → Lowers blood pressure.
Feedback Loop:
High BP → Increased baroreceptor activity → Reduced SNS → Lower BP.
Low BP → Decreased baroreceptor activity → Increased SNS → Higher BP.
how does noradrenaline cause arterial contraction
Receptor Activation:
Noradrenaline binds to alpha-1 adrenergic receptors on vascular smooth muscle cells.
Signal Transduction Pathway:
Activates Gq-protein.
Stimulates phospholipase C (PLC) enzyme.
Calcium Release:
PLC converts PIP2 into IP3 and DAG.
IP3 triggers calcium release from the sarcoplasmic reticulum.
Calcium-Dependent Contraction:
Increased intracellular calcium binds to calmodulin.
Activates myosin light chain kinase (MLCK).
MLCK phosphorylates myosin light chains, enabling contraction.
Sustained Contraction:
DAG activates protein kinase C (PKC), enhancing sensitivity to calcium and promoting sustained contraction.
Result:
Smooth muscle contracts, leading to arterial vasoconstriction and increased blood pressure.
adrenergic neuron blockers-Reserpine
-affects storage of noradrenaline.
-has uptake transporters which scoop up Noradrenaline from the synaptic space and repackages it back into vesicles to use again
-reserpine is taken up by the uptakers and binds to the noradrenaline pump blocking the function so less adrenaline packaged into vesicles and so less noradrenaline released less muscle contraction
adrenergic neuron blockers-guanethidine
-taken up by uptake 1, competes with NA to be taken up into storage vesicles and decreases NA stored due to higher affinity pump
-also interferes with action potential propagation via a different mechanisms
a1-adrenoreceptors treatment
-agonists- treatment of hypotension and shock
-e.g. methoxamine leads to an increase in bp through activation of smooth muscle a1-drenoreceptor
-anatagonist= treatment of hypertension e.g. razosin= blocks noradrenaline induced artery constrictions
central a2-adrenoceptors
-agonists = act pre synaptically to inhibit transmitter release
peripheral effects of a2 adrenoreceptors
- methyldopa can be targeted and form metylnoradrenaline.
-has no affect of a1 receptors but interacts with a2 adrenoreceptors causing hyperpolarization and stopping the nerve cells from firing
-agonist= e.g. clonidine, methyldopa -activate pre-junctional a2-receptors and so will block transmitter release from sympathetic nerves
calcium channel antagonist
-drugs target l-type calcium channels
mode of action of dihydropyridines
-target L-type calcium channels
-some increase calcium currents
-3 different modes of calcium channels :
0= cannot open depolarisation
1=low probablity
2-high probablity opening on depolarization
so DHPs stabilise channels into mode 0 so an inactive form and so act as an atagonist
-when act as an agonist? tehy change the calcium channels into mode 2
how is the endothelium able to control vascular systems
-the synthesis and release vof asoactive substances such as
-vasoconstrictors and vasodilators
endothelins
- 3 different endothelins 1,2 and 3 encoded by3 distinct gens
-have discrete distribution
-ET-1= only ET in endothelial cells and expressed by a wide variety of tissues
-ET-2 present in kidney
ET-3 present in brain,lungs and adrenal gland
production of ET-1
-endothelial cells have no storage vesicles and so controlled by Transcription/translation
-check lecture slides for diagram picture
-ET-1 causes arterial contraction
endothelium induced vasodilation
When the endothelial layer is present, it prevents the artery from contracting as much. This suggests that the endothelial cells help regulate the smooth muscle in the artery, controlling how much it contracts. The experiment was done using wire myography on a mesenteric arterial bed, measuring tension as a vasoconstrictor (substance causing contraction) is applied.
enodthelium derived relaxing factor
This slide explains how the endothelium (inner lining of blood vessels) regulates blood vessel relaxation. Endothelial cells produce nitric oxide (NO) in response to signals like ATP (through P2Y2 receptors). The process starts with L-arginine, which is converted into nitric oxide (NO) by nitric oxide synthase (NOS). NO then activates guanylate cyclase, leading to increased levels of cGMP. This, in turn, activates protein kinase G (PKG), which causes relaxation of the smooth muscle in the artery by reducing the activity of myosin light chain kinase (MLCK), resulting in vessel dilation.
prostacyclin synthesis and arterial relaxation
- prostacyclin (PGI2) helps relax arteries. Cyclooxygenase-1 (COX-1) in endothelial cells converts arachidonic acid into prostaglandin H2, which is then turned into prostacyclin (PGI2) by prostacyclin synthase. PGI2 binds to its receptor on smooth muscle cells, activating the Gαs protein. This activates adenylyl cyclase (AC), increasing cAMP levels. Elevated cAMP activates protein kinase A (PKA), which reduces the activity of myosin light chain kinase (MLCK), leading to smooth muscle relaxation and arterial dilation.
GPCR control of smooth musle
GPCR (G-protein coupled receptor) signaling controls smooth muscle contraction and affects blood vessel tone, diameter, and blood pressure. When an agonist (like noradrenaline, ATP, or angiotensin II) binds to a receptor on smooth muscle cells (e.g., α1AR, P2Y, AT1R, or ETAR), it activates Gαs and increases cAMP levels. This activates protein kinase A (PKA), which can reduce muscle contraction. In contrast, other signaling pathways (like L-type calcium channels and calmodulin activation) promote contraction by activating myosin light chain kinase (MLCK). The balance between vasoconstrictors and vasodilators (like PGI2 or NO) determines muscle tone and vessel diameter.
oxidative stress can cause endothelial cell dysfunction
NAD(P)H oxidase produces superoxide, which reacts with nitric oxide (NO) to form peroxynitrite, leading to endothelial damage. This reduces prostacyclin (PGI2) synthesis and increases the activity of matrix metalloproteinase-2 (MMP-2), further damaging the endothelium. Additionally, oxidative stress can activate the endothelin-1 (ET-1) pathway, where Big ET-1 is converted to ET-1, and angiotensin II (Ang II) activates the AT1 receptor (AT1R).
Role of the Kidney in regulation of blood pressure
-via Renin-Angiotensin system
-The Renin-Angiotensin system regulates blood pressure. When blood pressure drops, the kidneys release renin, which converts angiotensinogen to angiotensin I. ACE in the lungs converts angiotensin I to angiotensin II. Angiotensin II raises blood pressure by constricting blood vessels, releasing aldosterone (which increases sodium and water retention), and stimulating thirst.
Renin-Angiotensin system: Production of angiotensin II
The liver produces and releases angiotensinogen (452 amino acids).
The kidneys release renin, which converts angiotensinogen to angiotensin I (10 amino acids).
The endothelium has angiotensin-converting enzyme (ACE), which converts angiotensin I to angiotensin II (8 amino acids).
Angiotensin II helps regulate blood pressure.
Action of angiotensin 2
Actions of Angiotensin II
Angiotensin II receptors:
AT1 (in vascular and myocardial tissue)
AT2 (in adrenal medulla and possibly CNS)
AT1 receptors on smooth muscle activate Gq and PLC-β, leading to IP3 production, calcium release, and muscle contraction.
ACE inhibitors (e.g., captopril, ramapril) reduce peripheral resistance, but can cause a cough by interfering with bradykinin breakdown.
Angiotensin II antagonists (e.g., losartan) block AT1 receptors.
β1-adrenoceptor antagonists block β1-receptor activation, reducing renin release.
summary of Endothelium control of blood pressure
Vasoconstrictors: Angiotensin II, Endothelin 1
Vasodilators: Nitric oxide, Prostacyclin
Healthy Endothelium: Normal blood pressure of 120/70 mmHg with balanced vasoconstrictors and vasodilators.
Hypertension: Blood pressure > 140/90 mmHg, often due to excessive vasoconstrictor activity or insufficient vasodilation.
Hypotension: Blood pressure < 90/60 mmHg, possibly due to insufficient vasoconstriction or excessive vasodilation
