Cardiovascular hormonesCardiovascular hormones

Dr J KerDr J Ker

• Previous lecture: Previous lecture: MechanicalMechanical aspects, blood pressure, formulas…aspects, blood pressure, formulas…

• Now: Now: Hormonal Hormonal aspects of the aspects of the cardiovascular systemcardiovascular system

Hormonal interactions:Hormonal interactions:

• Heart----brainHeart----brain

• Brain----heartBrain----heart

• Heart----kidneyHeart----kidney

• Kidney----heartKidney----heart

Heart---brain:Heart---brain:

• Group of natriuretic peptides.Group of natriuretic peptides.

• ANP, BNP,C-typeANP, BNP,C-type

• Produced by atrial and ventricular Produced by atrial and ventricular myocardiummyocardium

• Produced in response to stretch, increased Produced in response to stretch, increased end-diastolic pressureend-diastolic pressure

• Physiological action: Acts as diuretic—Physiological action: Acts as diuretic—natriuretic peptidenatriuretic peptide

• Decrease blood pressureDecrease blood pressure

Clinical application:Clinical application:

• Diagnostic test for cardiac failureDiagnostic test for cardiac failure

• Opioid peptidesOpioid peptides

• Produced by heart—ventricular Produced by heart—ventricular myocardium.myocardium.

• Released during myocyte damage: Released during myocyte damage: MIMI

• Acts as natural pain killersActs as natural pain killers

• Angiotensin II.Angiotensin II.• Physiological action of angiotensin II:Physiological action of angiotensin II:• Vasoconstriction: Increase blood pressureVasoconstriction: Increase blood pressure• Vasoconstriction of efferent arteriole in kidney: Vasoconstriction of efferent arteriole in kidney:

Increase intraglomerular pressureIncrease intraglomerular pressure• Stimulate vascular growth—mitogenStimulate vascular growth—mitogen• Reabsorption of sodium in proximal tubuleReabsorption of sodium in proximal tubule• Stimulate production of aldosteroneStimulate production of aldosterone• Increase sympathetic outflowIncrease sympathetic outflow• Stimulate thirst: hypothalamusStimulate thirst: hypothalamus

Heart---kidney:Heart---kidney:

• Natriuretic peptidesNatriuretic peptides

• Angiotensin IIAngiotensin II

Kidney---heart:Kidney---heart:

• Renin-angiotensin-aldosterone Renin-angiotensin-aldosterone system:system:

• 2 pathways to angiotensin II 2 pathways to angiotensin II production:production:

• Via renin-angiotensin-aldosterone Via renin-angiotensin-aldosterone sustemsustem

• Via so-called non-ACE pathways.Via so-called non-ACE pathways.

Renin-angiotensin-aldosterone Renin-angiotensin-aldosterone system:system:

• Renin: An Renin: An enzymeenzyme produced by produced by kidney: juxtaglomerular apparatus.kidney: juxtaglomerular apparatus.

• In response to: decrease in BP, In response to: decrease in BP, increase in filtered sodium load.increase in filtered sodium load.

• Acts on: Acts on: AngiotensinogenAngiotensinogen. A . A protein produced by liver. Converts protein produced by liver. Converts to to angiotensin I.angiotensin I.

Angiotensin converting Angiotensin converting enzymeenzyme(ACE):(ACE):• Enzyme, produced by endothelium Enzyme, produced by endothelium

(especially pulmonary endothelium)(especially pulmonary endothelium)

• Converts Angiotensin I to angiotensin IIConverts Angiotensin I to angiotensin II

• 3 Genotypes:3 Genotypes:

• ACE-D/DACE-D/D

• ACE-I/IACE-I/I

• ACE-D/IACE-D/I

Non-ACE pathways:Non-ACE pathways:

• Various tissues: Heart, blood vessels, Various tissues: Heart, blood vessels, uterus, kidney:uterus, kidney:

• Able to convert AT II to AT II Able to convert AT II to AT II without without reninrenin

• Eg Eg chymasechymase• Also: Can produce AT II directlyAlso: Can produce AT II directly• Clinical implication: Drugs: ACE-Clinical implication: Drugs: ACE-

inhibitors vs AT-II receptor blockersinhibitors vs AT-II receptor blockers

AT-II receptors:AT-II receptors:

• > 7 known> 7 known

• 2 of clinical importance:2 of clinical importance:

• AT-II type I: Classic actions of angiotensin IIAT-II type I: Classic actions of angiotensin II

• AT-II type II: Importance in CV-AT-II type II: Importance in CV-development, fetusdevelopment, fetus

• AT-II blockers: Blocks only AT-II type I AT-II blockers: Blocks only AT-II type I receptorsreceptors

Aldosterone:Aldosterone:

• Hormone produced by adrenal cortexHormone produced by adrenal cortex

• Steroid hormoneSteroid hormone

• Production is stimulated by AT-IIProduction is stimulated by AT-II

• Physiological action:Physiological action:

• Reabsorption of sodium, excretion of Reabsorption of sodium, excretion of potassium and hydrogen:potassium and hydrogen:

• Kidney: Cortical collecting ductKidney: Cortical collecting duct

• Sweat, saliva, gastric juiceSweat, saliva, gastric juice

Conn syndrome:Conn syndrome:

• Tumor of adrenal cortex, producing Tumor of adrenal cortex, producing excess aldosterone:excess aldosterone:

• HypertensionHypertension

• HypokalaemiaHypokalaemia

• AlkalosisAlkalosis

Brain---heart:Brain---heart:

• Sympathetic nervous system:Sympathetic nervous system:• Acts on adrenal medulla: Increase Acts on adrenal medulla: Increase

catecholamines, increase in stroke catecholamines, increase in stroke volume and heart ratevolume and heart rate

• Acts on kidney: Increase production Acts on kidney: Increase production of reninof renin

• Other hormones: Growth hormone: Other hormones: Growth hormone: Trophic effect on heartTrophic effect on heart

Endothelium:Endothelium:

• An An organorgan

• 2`nd largest organ in body2`nd largest organ in body

• Largest=fatLargest=fat

• Why an organ: It produces hormonesWhy an organ: It produces hormones

• Weight of endothelium +/- 1.5 kgWeight of endothelium +/- 1.5 kg

• Endothelium: Endothelium: 4 groups of 4 groups of functions:functions:

• Maintains balance between Maintains balance between vasoconstriction and vasoconstriction and vasodilatation:vasodilatation:

• NO, bradykinin, ANP: VasodilatationNO, bradykinin, ANP: Vasodilatation

• AT-II, thromboxane A2: AT-II, thromboxane A2: VasoconstrictionVasoconstriction

• Maintains balance between Maintains balance between thrombosis and fibrinolysis:thrombosis and fibrinolysis:

• Tissue factor (factor III): ThrombosisTissue factor (factor III): Thrombosis

• T-PA: Tissue type plasminogen T-PA: Tissue type plasminogen activator: Fibrinolysisactivator: Fibrinolysis

• Maintains balance between Maintains balance between inflammation and anti-inflammation and anti-inflammatory mechanisms.inflammatory mechanisms.

• Endothelium produces adhesion Endothelium produces adhesion molecules: ICAM, PECAM, VECAM etcmolecules: ICAM, PECAM, VECAM etc

• Maintains balance between Maintains balance between growth and apoptosis:growth and apoptosis:

• Angiotensin II: A growth factor, Angiotensin II: A growth factor, mitogen, causes hypertrophy of mitogen, causes hypertrophy of arterial intimaarterial intima