Blood Pressure Regulation
• BP increases due to two factors: increased cardiac output (HR x SV) and increased peripheral
resistance. This can be explained by the equation
MAP = CO x TPR
• Peripheral resistance is determined by three factors
1. Blood viscosity (thickness) – RBC and albumin elevate viscosity
2. Vessel length – farther liquid travels in tube, more cumulative friction it encounters
3. Vessel radius – most powerful influence over flow
High Pressure (Arterial) Baroreceptor – Fast Response
• Located in carotid sinus and aortic arch
• Mechanoreceptors in these areas will activate from increased stretch, send messages to medulla via
CN IX (innervates carotid sinus) and CN X (innervates aortic arch) and cause
i.
Inhibition of vasomotor centre – leads to vasodilation
ii.
Stimulation of cardioinhibitory centre and inhibition of cardioacceleratory centre – this
leads to decreased heart rate (decreased cardiac output)
• Will be opposite when BP drops
Low Pressure Baroreceptors – Slower Response
• Located in walls of major veins (IVC & SVC) and atria of the heart
• They are involved in the regulation of blood volume
• Decrease in blood volume will cause
i.
Stimulation of osmorecpetors causing increased secretion of ADH
ii.
Increase in Renin-Angiotenisn-Aldosterone pathways
iii.
Increase in sympathetic tone (vasomotor centre activation)
Atrial Natriuretic Peptides
• Atrial distension due to increase in BP will cause the release of Natriuretic Peptide
• This hormone causes the following
• Medulla Oblongata causes a drop in blood pressure due to vasodilation of blood vessels
Juxtaglomerular Apparatus
• This apparatus incorporates macula densa cells and juxtaglomerular cells (aka granular cells)
i.

Increased GFR (due to high BP)
↑ GFR  ↑ flow through tubules & ↑ NaCl reabsorption  sensed by macula densa cells
which release paracrine signal to afferent arterioles  afferent arterioles constrict = ↓ GFR
ii.

Decreased GFR (due to low BP)
↓ GFR  ↓ flow rate through tubules & ↓ NaCl in tubules due to body trying to reabsorb
as much of it as it can  sensed by macula densa cells which:
o
o
Trigger dilation of afferent arteriole to increase blood flow to glomerulus
Signal juxtaglomerular cells to release rennin
Renin-Angiotenisn-Aldosterone System
• Renin secreted by juxtaglomerular cells converts angiotensinogen (a blood protein produced by
liver) into angiotensin I
• Lungs and Kidney’s produce Angiotensin converting enzyme (ACE) to convert Angiotenisn I to
Angiotensin II (the active hormone)
• Angiotenisn II increases BP through various mechanisms (see diagram below)
Note: In the diagram - vassopresin is also called ADH
Note: Angiotenis II is also a hypertrophogenic agent. It stimulates myocyte and smooth muscle
hypertrophy in the arterioles. Could lead to constriction of arterioles leading to increased BP
Other BP Mechanisms Learnt in Week 1
Chemoreceptors
• Detect ↓ PaO2, ↓ pH or ↑ CO2  ↑ activity of vasomotor centre  ↑ MAP and thus, ↑ flow rate
CNS Ischemic Response
• Activated when MAP < 60 mmHg  ↑vasomotor and cardio-stimulatory neurons signalling 
↑ TPR and ↑ HR  ↑ MAP
Capillary Fluid Shift
• ↑BP → ↑hydrostatic & oncotic pressure → ↑fluid from capillaries into interstitium → ↓blood
volume → ↓venous return → ↓CO → ↓BP
Hypertension
• Hypertension = sustained blood pressure of >140/90 mmHg
Classification
Primary (Essential or Idiopathic) Hypertension
• Accounts for 90-95% of all hypertension presentations
• The precise aetiology is unknown
• Risk factors involved are
Obesity
Smoking
Genetics
Aging
Hyperlipidemia
Sleep apnoea
Increased salt intake
Oral contraceptive
• Insulin resistance can cause
 ↓ endothelial release of NO and other vasodialtors
 Na & H2O retention in kidney
 Overeactivity of RAAS and SNS
• Genetic factors such as defect in sodium secretion mechanism in kidney  sodium retained 
water retained  ↑ in blood volume  ↑ BP
• Inhibition of Na/K pump in kidney and vessel wall cells
Secondary Hypertension
• Accounts for 5-10% of all cases
• Hypertension occurs due to a systemic disease (it is a symptom of the systemic disease)
1. Renal
a. Renal artery stenosis
b. Renin-secreting tumour
c. Glomerular nephritis
d. Polycystic kidney disease
2. Endocrine
a. Phaeochromocytoma (↑ catecholamines)
b. Cushings (↑ cortisol)
c. Conn’s Syndrome (↑ aldosetrone)
d. Thyrotoxicosis (from hyperthyroisdism)
3. Cardiovacular
a. Coarctation of the aorta
4. Neurological
a. Stress (↑ SNS)
5. Drugs
a. NSAIDs
b. Oral Contraceptive
c. Corticosteroids
6. Pregnancy
Malignant Hypertension
• Affects about 1% of people with high BP
• Malignant hypertension = intense spasm of arteries due to failure of normal autoregulation
• It comes on very suddenly and is a medical emergency
• Systolic can go > 210 mmHg and diastolic can go > 130 mmHg
• Will get retinal hemorrhage, increased intracranial pressure, kidney damage
Risk Factors for Hypertension
 Age – BP increases with age
 Race – Asians and African Americans more prone to elevated BP
 Genetic - ↑ incidence if first degree relatives have hypertension
 Gender – Males have higher BP
 Diet – particularly high salt and alcohol intake
 Smoking – nicotine causes blood vessels to constrict
 Obesity
Complications of Hypertension
1.


Blood vessels
Damage of vessel walls leading to arteriosclerosis
Distension of vessel walls leading to aneurysm
2.



Heart
Left ventricular hypertrophy
Congestive heart failure
MI
3.



Brain
Stroke
Aneurysm
Haemorrhage
4.


Eyes
Thickening of vessel walls
Blurred or patchy vision
5.


Kidneys
Can get prteinuria
Renal failure
Treatment of Hypertension
• Of the 10 most prescribed drugs, 8 are cardiovascular drugs
• Treatment based on CV risk and BP. Before beginning treatment confirm grade of hypertension
 High CV risk (> 15% next 5 years) or Grade 3 hypertension – start antihypertensive and
implement lifestyle change
 Moderate CV risk (10-15% next 5 years) – lifestyle change and reassess in 6 months
 Low CV risk (< 10% next 5 years) - lifestyle change and reassess in 12 months
Note: if lifestyle change has not lowered BP in low or moderate, start antihypertensive
• Interesting Fact – lowering systolic BP by 20 mmHg or diastolic BP by 10 mmHg reduces risk of CV
event by 25% and stroke by 33%
ACE Inhibitors
• Are commonly used as first-line therapy
• E.g’s captopril, perindopril, ramipril etc (anything ending in pril)
• MOA = inhibit ACE in RAAS system  no formation of angiotenisn II
• It will also cause ↓ breakdown of bradykinin. (↑Bradykinin  ↑ NO release  ↑ vasodialtion)
• Side Effects = dry cough (most common) due to accumulation of bradykinin, first dose hypotension
• Contraindications
 Renal stenosis – kidney relies on high BP and angiotensin II to maintain GFR
 Hyperkalaemia - causes K+ retention due to reduced aldosterone secretion
 Pregancy – foetal toxicity
• Be aware of drug-drug interactions (NSAIDs – reduce effectiveness, K+ supplements and K+ sparing
diuretics will lead to hyperkalaemia)
Angiotenisn II Receptor Antagonists
• More expensive than ACE inhibitors but they are well tolerated, no cough and used in younger
patients + those with type 2 diabetes
• E.g’s losartan, valsartan etc (anything ending in sartan)
• MOA = Block actions of angiotensin II at angiotenisn AT1 receptor
• Same contraindications as ACE Inhibitors
β-Adrenoceptor Antagonist
• Not used very often used for hypertension and not as well tolerated as above drugs
• There are 3 β-adrenoceptors and cardioselective (β1) β-blockers are preferable
• E.g. atenolol, metoprolol, etc (anything ending in olol)
• MAO unknown but may be due to
 Reduction in peripheral resistance
 Inhibition of rennin release (β1 in kidney)
 Reduce sympathetic activity
• Side effects = cold hands and feet, fatigue, mask sympathetic response to hypoglycaemia
(tachycardia) in diabetics
• Contraindications
 Never use non-selective β-blockers in asthmatic or COPD petients
 Athletes and physically active people
 Cardiac depression
Calcium Channel Blockers
• Are commonly used to treat hypertension and because side effects directly opposite to that of βblockers, they are often used in conjunction with β-blockers
• MOA = block voltage gated calcium channels. They show selectivity between vascular and cardiac
channels to cause reduction of peripheral resistance and reduction of cardiac output respectively
• E.g. amlodipine, felodipine (anything ending in dipine) are selective for Ca channels on blood
vessels. They can cause reflex tachycardia but are the main CCBs used as antihypertensive
• E.g. verapamil is cardioselective (but mainly used as antiarrhythmic)
• Side effects = flushing, headache + ankle oedema (due to vasodilation), constipation, bradycardia
Thiazide Diuretics
• Commonly first line treatment in mild-moderate hypertension in elderly patients
• E.g. hydrocholorothiazide (anything ending in thiazide)
• MOA = initially fall in Bp due to diuresis.
 Thiazide-like diuretics inhibit agonist induced vasoconstriction by casuing calcium
desensitisation in smooth muscle cells
Less Commonly Used Agents
α-Adrenoceptor antagonists – e.g. doxazosin, prazosin
MOA = block α1 adrencoeptor leading to opposition of muscle contraction
Centrally acting agents – e.g. moxonidine, methyldopa
MOA = α2 agonist
Direct-acting vasodilators – e.g. hydralazine, minoxidil
Used in emergencies and when show resistance to other drugs
Drugs of Choice Diagram
Treatment Failure
• Compliance failure (20% patients don’t pick up second prescription, 50% discontinue with 1-2 years
of initiation)
• Conn’s syndrome
• Renovascular disease
• White coat hypertension
Lifestyle Ways to Reduce Hypertension
• Weight loss  1 % reduction in weight lowers systolic BP by 1 mmHg, 10Kg can reduce BP by 6-10
mmHg
• Salt restriction  4g/day or less (average = 9g)
• Avoid binge drinking, have two alcohol free days per week, max 2 drinks per day (M) or 1 per day (F)
• 30 mins of moderate exercise on most days of week
Effects of long term high blood pressure
Arteries
• Will cause damage to lining or arteries (endothelium) leading to a cascade of events that casue
arteriosclerosis
• High pressure moving through weak artery causing a section of it to enlarge and form a bulge
(aneurysms) that can potentially rupture
Heart
• Coronary artery disease – blood supply to heart affected which can lead to a variety of problems
depending on what area becomes ischemic
• Ventricular hypertrophy – which eventually leads to heart failure