Controlling Blood Pressure

Question 1

What are the equations for maBP and CO?

Answer 1

Pressure = flow x resistance
Mean arterial BP = CO x TPR
CO = SV x HR

Question 2

How is blood pressure regulated in the short term?

Answer 2

Short term regulation is done via the baroreceptor reflex. This is done by adjusting the sympathetic and parasympathetic inputs to the heart to alter cardiac output. Adjust sympathetic input to peripheral resistance vessels to alter TPR.

Question 3

Where are the baroreceoptors found and how do they work?

Answer 3

Baroreceptors are found in the carotid sinus and aortic arch. Stretch receptors that are sensitive to stretch. Stretch detected in medulla part of the brain stem – cardiovascular control centre. (also works for low pressure as less stretch).

Question 4

Why wont these baroroceptors work for sustained changes in BP?

Answer 4

Don’t work for sustained regulation as the baroreceptors accommodate for lengthy high pressure so eventually get used to it. Baroreceptors change their threshold.

Question 5

In general terms how is blood pressure controlled in the longer term?

Answer 5

Control of extracellular fluid volume controls plasma volume. Water follows Na+ therefore controlling total body Na levels controls plasma volume and so BP.

Question 6

What does renin do?

Answer 6

Renin breaks down angiotensinogen into angiotensin I (not physiologically active), ACE (angiotensin converting enzyme) breaks this down to Angiotensin II. ACE isn’t under physiological control. Only thing under control by the body is the release of renin.

Question 7

What does Angiotensin II do?

Answer 7

Angiotensin II does 3 main things
•Powerful vasoconstrictor
•Stimulates the kidneys to reabsorb Na+
•Stimulates aldosterone release from the adrenal cortex. Aldosterone also stimulate the kidneys to retain more Na+
•Increases thirst sensation by stimulating ADH release
•Increased NA release from sympathetic NS

Angiotensin II acts at G proteins coupled receptors AT1 and AT2. Main actions are via the AT1 receptors.

Question 8

Where is renin released from?

Answer 8

Renin is released form granular cells of juxtaglomerular apparatus.

Question 9

What stimulates renin’s release?

Answer 9

1. If there is decreased NaCl at the macula densa cells then they will release paracrine substances (prostaglandins or NO) which stimualte the granular cells to release renin.
2. Sympathetic innervation of these granular cells also causes release of renin if the overall circualting volume decreases
3. Reduced perfusion pressure in the kidney causes release of renin when detected by the granular cells.

Question 10

What action does Angiotensin II have on the kidneys?

Answer 10

Vasoconstriction of the afferent and efferent arteriole reducing GFR. Enhanced Na+ reabsorption at the PCT by stimulation of the Na-H exchanger (NHE3) in the apical membrane.

Question 11

What are the actions of Aldosterone on the kidney

Answer 11

Aldosterone acts on the principle cells of the collecting ducts. This stimulates Na+ and therefore water reabsorption. Activates apical Na+ channel (ENaC) and apical K+ channel. Also, increases basolateral Na+ extrusion via Na/K/ATPase. It does this by increasing expression of the channels by the cell. Steroid hormones act directly on the nucleus.

Question 12

Why do some people get coughs on ACE inhibitors?

Answer 12

ACE is also known as kininase II which breaks down the vasodilator Bradykinin into peptide fragments. When on ace inhibitors some people get a dry cough this is thought to be because of the increased bradykinin.

Question 13

How does the sympathetic NS control BP?

Answer 13

High levels of sympathetic stimulation will reduce the renal blood flow via vasoconstriction of arterioles decreasing the GFR. It also activates the Apical Na/H exchanger and basolateral Na/K ATPase in the PCT. Finally, it stimulates renin release from the Granular cells of the afferent arteriole as mentioned earlier.

Question 14

How is ADH involved in BP control

Answer 14

ADh increases water reabsorption in the distal nephron (AQP2). ADH is stimulated to be released by increase in plasma Osmolarity or severe hypovolaemia. It also stimulates Na+ reabsorption by acting on the thick ascending limb to stimulate the apical Na/K/2Cl co transporter. Finally, is causes vasoconstriction and so is known as arginine vasopressin.

Question 15

What is atrial natriuretic peptide?

Answer 15

Atrial natriuretic peptide promotes Na+ excretion, it is synthesised and stored in atrial myocytes and is released in response to stretch. They act as low pressure volume sensors (because they’re on the low-pressure side of the system and detect volume changes) if volume is decreased this inhibits the release of ANP and supports BP.

Question 16

How does ANP exert it’s effects?

Answer 16

ANP causes vasodilation of the afferent arteriole increasing blood flow to the GFR. It also inhibits Na+ reabsorption along the nephron. It acts in opposite direction to other neurohumoral regulators by causing natriuresis (loss of sodium).

Question 17

What role do porostaglandins play in controlling blood pressure?

Answer 17

These act as vasodilators. Locally acting prostaglandins (primarily PEG2) enhance GFR and reduce Na+ reabsorption. They may have a protective function acting as a buffer to excessive vasoconstriction by the SNS and RAA. Especially important when Ang II is high. They can be used to maintain renal blood flow and GFR in the presence of vasoconstrictors.

Question 18

What issues can NSAIDS have when renal perfusion is compromised?

Answer 18

NSAIDs (non-steroidal anti-inflammatory drugs) inhibit cyclo-oxygenase (COX) pathway involved in formation of prostaglandins. If they are administered when renal perfusion is compromised can further decrease GFR leading to renal failure.

Question 19

What role do Dopamine play in controlling blood pressure?

Answer 19

This is formed locally in the kidneys from circulating L-DOPA. Dopamine receptors are present on renal blood vessels and cells of the PCT and TAL. Dopamine also causes vasodilation increasing renal blood flow. Dopamine also reduces reabsorption of NaCl by inhibiting NH exchanger and Na/K ATPase in principle cells of the PCT and TAL.

Very high dose of dopamine acts on adrenergic receptors causing vasoconstriction.

Question 20

What is essential primary hypertension?

Answer 20

When it isn’t known what causes a patient to have hypertension.

It is thought it could be due to genetics as it runs in families, environmental factors or potentially a dysfunction of dopamine receptors.

Question 21

What are the different stages of hypertension?

Answer 21

Stage 1 = 140/90
Stage 2 = 160/100
Severe Hypertension = 180/110

Question 22

What causes secondary hypertension?

Answer 22

• Reno-vascular disease – occlusion of the renal artery causing a fall in perfusion pressure. This causes increase renin production leading to vasoconstriction and Na+ retention at the other kidney.
• Renal parenchymal disease – earlier stage of this disease may lead to a loss of vasodilator substances, in later stages inadequate glomerular filtration causing volume-dependant hypertension.
• Chronic renal disease
• Conn’s syndrome (Aldosteronism) – aldosterone secreting adenoma leading to hypertension and hypokalaemia.
• Cushing’s syndrome – excess secretion of glucocorticoid that acts on aldosterone receptors.
• Pheochromocytoma – tumour of the adrenal medulla secreting (nor) – adrenaline

Question 23

Why is hypertension important to catch?

Answer 23

Hypertension is important to treat because it is the silent killer – it is asymptomatic (unless extremely high) but has damaging effects on the heart and vasculature leading to MI, Stroke, renal failure and retinopathy.

Question 24

How do we treat hypertension?

Answer 24

Lower stroke volume, lower heart rate or decrease the TPR
•ACE inhibitors (dry cough) or ANGII receptor antagonists are just as effective as they both prevent vasoconstriction and the release of aldosterone
•Vasodilators e.g. L-type Ca channel blockers which reduce Ca++ entry to vascular smooth muscle, can use alpha1 receptor blockers reducing sympathetic tone but this may cause postural hypotension.
•Diuretics
•Best treatment is a lifestyle change targeting diet, exercise, reducing Na+ and alcohol intake

Question 25

When do we and don’t we use Beta blockers in treatment of hypertension

Answer 25

We do not use beta blockers because they reduce sympathetic output which reduces heart rate and contractility but will be used if there is a history of MI as well as hypertension.