Endocrine regulation of vascular tone

Question 1

What are the functions of blood vessels?

Answer 1

• Oxygenated, nutrition and removal of waste products
• Carriage of blood- without haemorrhage or thrombosis
• Maintenance of a steady head of prefusion pressure

Question 2

What is a hormone?

Answer 2

A chemical substance produced in the body that controls and regulates the activity of certain cells or organs

Question 3

What are the types of hormones?

Answer 3

Endocrine (classical)
Paracrine
Autocrine

Question 4

Describe endocrine hormones

Answer 4

In distant cells/ organs

Thyroxine, calcitonin, adrenaline, oestrogen, testosterone

Question 5

Describe paracrine hormones

Answer 5

In adjacent cells/ organs

Nitric oxide, endothelin, noradrenaline

Question 6

Describe autocrine hormones

Answer 6

In the same cell/ organ

Endothelin, noradrenaline

Question 7

What classical vasoactive hormones are involved in the renin-angiotensin system?

Answer 7

Angiotensin 11 (ANG 11)/ Aldosterone (Aldo)

Question 8

What classical vasoactive hormones are involved in the SNS?

Answer 8

Noradrenaline/ adrenaline

Question 9

What classical vasoactive hormones are involved in the hypothalamic regulation?

Answer 9

Arginine Vasopressin/ Anti-diuretic hormone

Question 10

What classical vasoactive hormones are involved in the cardiac stretch receptors?

Answer 10

Natriuretic peptides- atrial and brain

Question 11

Name other classical vasoactive hormones

Answer 11

Apelin, Ghrelin, Relaxin, Uromodulin, Urotensin 11

Question 12

How is adrenaline involved in the fight-or-flight repsonse?

Answer 12

Tachycardia, increased cardiac contractility (beta 1), increased muscle blood flow, bronchodilation (beta 2), hypertension
Adrenal gland

Question 13

How is noradrenaline involved in the fight-ot-flight response?

Answer 13

Peripheral vasoconstriction (alpha 1), renal and splanchnic vasoconstriction, hypertension
Peripheral neurotransmitter

Question 14

What hormones retain body sodium?

Answer 14

ANG11, Aldo

Question 15

What hormones excrete body sodium?

Answer 15

ANP/BNP

Question 16

What hormones retain body water?

Answer 16

ADH/AVP (ANG11, Aldo)

Question 17

What hormones excrete body water?

Answer 17

ANP/BNP

Question 18

What hormones increase cardiac output?

Answer 18

AD

Question 19

What hormones decrease cardiac output?

Answer 19

NA

Question 20

What hormones increase blood pressure?

Answer 20

NA, AD, ANG11, Aldo

Question 21

What hormones decrease blood pressure?

Answer 21

ANP/BNP

Question 22

What medical conditions are mediated by ANG11/ Aldo?

Answer 22

Hypertension
Heart Failure
Diabetic Nephropathy

Question 23

What medical conditions are mediated by AD/ NA?

Answer 23

Hypertension
Heart Failure
Ischaemic Heart Disease

Question 24

What medical conditions are mediated by AVP (ADH)?

Answer 24

Hyponatraemia (low blood Na+) in heart failure

Hepatic Cirrhosis and SIADH (syndrome of inappropriate ADH production)

Question 25

What types of drugs are used in hypertension?

Answer 25

ACE inhibitors, angiotensin receptor blockers, mineralocorticoid receptor blockers, alpha-adrenoreceptor blockers, beta-adrenoreceptor blockers

Question 26

What types of drugs are used in heart failure?

Answer 26

ACE inhibitors, angiotensin receptor blockers, mineralocorticoid receptor blockers, beta-adrenoreceptor blockers, ANP/BNP analogues

Question 27

What types of drugs are used in angina pectoris?

Answer 27

Beta-adrenoreceptor blockers

Question 28

What are the 'new' endothelial hormones?

Answer 28

Nitric Oxide | Endothelin-1

Question 29

What effect does ACh have on blood cells

Answer 29

Causes endothelial cells to release NO so relaxes blood vessels

Question 30

What are the traditional risk factors of endothelium damage?

Answer 30

``` Metabolic factors Blood flow Adhesion Thrombosis Vascular tone Proliferation Permeability Inflammation Genetic factors ```

Question 31

What are the causes of endothelial dysfunction?

Answer 31

Hyperlipidaemia, hypertension, diabetes mellitus, smoking, menopause, hyperhomocysteinaemia, poor diet, obesity/ inactivity, ageing LESS NO, MORE ET-1

Question 32

What are the roles of NO and ET-1?

Answer 32

``` NO= vasodilator, anti-aggregatory ET-1= vasoconstrictor, pro-aggregatory ```

Question 33

Describe how NO is generated?

Answer 33

L-arginine- NO synthase- NO O2 requirement L-citrulline by-product

Question 34

Describe the action of NO

Answer 34

N0 GTP converted to cGMP via NO-haem guanylate cyclase Relaxation

Question 35

How is NO stimulated?

Answer 35

Shear stress/ blood flow, acetylcholine, bradykinin, Substance P= Ca2+ release= NO synthase activity

Question 36

How else is NO sourced?

Answer 36

Organic nitrates/ nitroprusside

Question 37

How is NO generated inhibited?

Answer 37

L-Monomethyl arginine | Inhibits NO synthase

Question 38

Benefits of NO

Answer 38

Vasodilatory Anti-proliferative Anti-inflammatory Anti-platelet

Question 39

Name NO therapeutics

Answer 39

Organic nitrates Nitrosothiols GC stimulators/ activators PDE5 inhibitors (phosphodiesterase type 5)

Question 40

How does dietary nitrate lead to NO generation?

Answer 40

- Ingestion of dietary nitrate - Nitrate absorbed from stomach and small intestine - Concentration of nitrate in the salivary gland - Nitrate excreted by kidneys - Lingual bacteria reduce nitrate to nitrite - Acidic conditions of stomach reduce nitrite to NO - NO and nitrite diffuse into portal circulation= NO oxidised to nitrite - Nitrite transported in arterial circulation - Nitrite reduced to NO in resistance vessels, causing vasodilation and lowering blood pressure

Question 41

Describe the actions of ET-1

Answer 41

PrepoET-1= Big ET-1 and ECE= ET-1= ET(A)R and ET(B)R

Question 42

What are the major actions at the ET(A) Receptor?

Answer 42

Vasoconstriction, hypertension, arterial stiffness, endothelial dysfunction, insulin resistance, aldosterone release, atherosclerosis, inflammation, fibrosis

Question 43

What are the major actions at the ET(B) Receptor?

Answer 43

Vasodilation, ET-1 clearance, Natriuresis

Question 44

What gaseous mediators could be used in the future?

Answer 44

CO, H(2)S, NO

Question 45

How can endothelin dysfunction be reversed?

Answer 45

May be achieved by diet, exercise, new drugs, crucial therapeutic target in vascular disease