Endocrine regulation of vascular tone Flashcards
What are the functions of blood vessels?
- Oxygenated, nutrition and removal of waste products
- Carriage of blood- without haemorrhage or thrombosis
- Maintenance of a steady head of prefusion pressure
What is a hormone?
A chemical substance produced in the body that controls and regulates the activity of certain cells or organs
What are the types of hormones?
Endocrine (classical)
Paracrine
Autocrine
Describe endocrine hormones
In distant cells/ organs
Thyroxine, calcitonin, adrenaline, oestrogen, testosterone
Describe paracrine hormones
In adjacent cells/ organs
Nitric oxide, endothelin, noradrenaline
Describe autocrine hormones
In the same cell/ organ
Endothelin, noradrenaline
What classical vasoactive hormones are involved in the renin-angiotensin system?
Angiotensin 11 (ANG 11)/ Aldosterone (Aldo)
What classical vasoactive hormones are involved in the SNS?
Noradrenaline/ adrenaline
What classical vasoactive hormones are involved in the hypothalamic regulation?
Arginine Vasopressin/ Anti-diuretic hormone
What classical vasoactive hormones are involved in the cardiac stretch receptors?
Natriuretic peptides- atrial and brain
Name other classical vasoactive hormones
Apelin, Ghrelin, Relaxin, Uromodulin, Urotensin 11
How is adrenaline involved in the fight-or-flight repsonse?
Tachycardia, increased cardiac contractility (beta 1), increased muscle blood flow, bronchodilation (beta 2), hypertension
Adrenal gland
How is noradrenaline involved in the fight-ot-flight response?
Peripheral vasoconstriction (alpha 1), renal and splanchnic vasoconstriction, hypertension Peripheral neurotransmitter
What hormones retain body sodium?
ANG11, Aldo
What hormones excrete body sodium?
ANP/BNP
What hormones retain body water?
ADH/AVP (ANG11, Aldo)
What hormones excrete body water?
ANP/BNP
What hormones increase cardiac output?
AD
What hormones decrease cardiac output?
NA
What hormones increase blood pressure?
NA, AD, ANG11, Aldo
What hormones decrease blood pressure?
ANP/BNP
What medical conditions are mediated by ANG11/ Aldo?
Hypertension
Heart Failure
Diabetic Nephropathy
What medical conditions are mediated by AD/ NA?
Hypertension
Heart Failure
Ischaemic Heart Disease
What medical conditions are mediated by AVP (ADH)?
Hyponatraemia (low blood Na+) in heart failure
Hepatic Cirrhosis and SIADH (syndrome of inappropriate ADH production)
What types of drugs are used in hypertension?
ACE inhibitors, angiotensin receptor blockers, mineralocorticoid receptor blockers, alpha-adrenoreceptor blockers, beta-adrenoreceptor blockers
What types of drugs are used in heart failure?
ACE inhibitors, angiotensin receptor blockers, mineralocorticoid receptor blockers, beta-adrenoreceptor blockers, ANP/BNP analogues
What types of drugs are used in angina pectoris?
Beta-adrenoreceptor blockers
What are the ‘new’ endothelial hormones?
Nitric Oxide
Endothelin-1
What effect does ACh have on blood cells
Causes endothelial cells to release NO so relaxes blood vessels
What are the traditional risk factors of endothelium damage?
Metabolic factors Blood flow Adhesion Thrombosis Vascular tone Proliferation Permeability Inflammation Genetic factors
What are the causes of endothelial dysfunction?
Hyperlipidaemia, hypertension, diabetes mellitus, smoking, menopause, hyperhomocysteinaemia, poor diet, obesity/ inactivity, ageing
LESS NO, MORE ET-1
What are the roles of NO and ET-1?
NO= vasodilator, anti-aggregatory ET-1= vasoconstrictor, pro-aggregatory
Describe how NO is generated?
L-arginine- NO synthase- NO
O2 requirement
L-citrulline by-product
Describe the action of NO
N0
GTP converted to cGMP via NO-haem guanylate cyclase
Relaxation
How is NO stimulated?
Shear stress/ blood flow, acetylcholine, bradykinin, Substance P= Ca2+ release= NO synthase activity
How else is NO sourced?
Organic nitrates/ nitroprusside
How is NO generated inhibited?
L-Monomethyl arginine
Inhibits NO synthase
Benefits of NO
Vasodilatory
Anti-proliferative
Anti-inflammatory
Anti-platelet
Name NO therapeutics
Organic nitrates
Nitrosothiols
GC stimulators/ activators
PDE5 inhibitors (phosphodiesterase type 5)
How does dietary nitrate lead to NO generation?
- 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
Describe the actions of ET-1
PrepoET-1= Big ET-1 and ECE= ET-1= ET(A)R and ET(B)R
What are the major actions at the ET(A) Receptor?
Vasoconstriction, hypertension, arterial stiffness, endothelial dysfunction, insulin resistance, aldosterone release, atherosclerosis, inflammation, fibrosis
What are the major actions at the ET(B) Receptor?
Vasodilation, ET-1 clearance, Natriuresis
What gaseous mediators could be used in the future?
CO, H(2)S, NO
How can endothelin dysfunction be reversed?
May be achieved by diet, exercise, new drugs, crucial therapeutic target in vascular disease
