Cardiovascular hormones Dr J Ker

Previous lecture: Mechanical aspects, blood pressure, formulas… Previous lecture: Mechanical aspects, blood pressure, formulas… Now: Hormonal aspects of the cardiovascular system Now: Hormonal aspects of the cardiovascular system

Hormonal interactions: Heart----brain Heart----brain Brain----heart Brain----heart Heart----kidney Heart----kidney Kidney----heart Kidney----heart

Heart---brain: Group of natriuretic peptides. Group of natriuretic peptides. ANP, BNP,C-type ANP, BNP,C-type Produced by atrial and ventricular myocardium Produced by atrial and ventricular myocardium Produced in response to stretch, increased end- diastolic pressure Produced in response to stretch, increased end- diastolic pressure Physiological action: Acts as diuretic—natriuretic peptide Physiological action: Acts as diuretic—natriuretic peptide Decrease blood pressure Decrease blood pressure

Clinical application: Diagnostic test for cardiac failure Diagnostic test for cardiac failure

Opioid peptides Opioid peptides Produced by heart—ventricular myocardium. Produced by heart—ventricular myocardium. Released during myocyte damage: MI Released during myocyte damage: MI Acts as natural pain killers Acts as natural pain killers

Angiotensin II. Angiotensin II. Physiological action of angiotensin II: Physiological action of angiotensin II: Vasoconstriction: Increase blood pressure Vasoconstriction: Increase blood pressure Vasoconstriction of efferent arteriole in kidney: Increase intraglomerular pressure Vasoconstriction of efferent arteriole in kidney: Increase intraglomerular pressure Stimulate vascular growth—mitogen Stimulate vascular growth—mitogen Reabsorption of sodium in proximal tubule Reabsorption of sodium in proximal tubule Stimulate production of aldosterone Stimulate production of aldosterone Increase sympathetic outflow Increase sympathetic outflow Stimulate thirst: hypothalamus Stimulate thirst: hypothalamus

Heart---kidney: Natriuretic peptides Natriuretic peptides Angiotensin II Angiotensin II

Kidney---heart: Renin-angiotensin-aldosterone system: Renin-angiotensin-aldosterone system: 2 pathways to angiotensin II production: 2 pathways to angiotensin II production: Via renin-angiotensin-aldosterone sustem Via renin-angiotensin-aldosterone sustem Via so-called non-ACE pathways. Via so-called non-ACE pathways.

Renin-angiotensin-aldosterone system: Renin: An enzyme produced by kidney: juxtaglomerular apparatus. Renin: An enzyme produced by kidney: juxtaglomerular apparatus. In response to: decrease in BP, increase in filtered sodium load. In response to: decrease in BP, increase in filtered sodium load. Acts on: Angiotensinogen. A protein produced by liver. Converts to angiotensin I. Acts on: Angiotensinogen. A protein produced by liver. Converts to angiotensin I.

Angiotensin converting enzyme (ACE): Enzyme, produced by endothelium (especially pulmonary endothelium) Enzyme, produced by endothelium (especially pulmonary endothelium) Converts Angiotensin I to angiotensin II Converts Angiotensin I to angiotensin II 3 Genotypes: 3 Genotypes: ACE-D/D ACE-D/D ACE-I/I ACE-I/I ACE-D/I ACE-D/I

Non-ACE pathways: Various tissues: Heart, blood vessels, uterus, kidney: Various tissues: Heart, blood vessels, uterus, kidney: Able to convert AT II to AT II without renin Able to convert AT II to AT II without renin Eg chymase Eg chymase Also: Can produce AT II directly Also: Can produce AT II directly Clinical implication: Drugs: ACE-inhibitors vs AT-II receptor blockers Clinical implication: Drugs: ACE-inhibitors vs AT-II receptor blockers

AT-II receptors: > 7 known > 7 known 2 of clinical importance: 2 of clinical importance: AT-II type I: Classic actions of angiotensin II AT-II type I: Classic actions of angiotensin II AT-II type II: Importance in CV-development, fetus AT-II type II: Importance in CV-development, fetus AT-II blockers: Blocks only AT-II type I receptors AT-II blockers: Blocks only AT-II type I receptors

Aldosterone: Hormone produced by adrenal cortex Hormone produced by adrenal cortex Steroid hormone Steroid hormone Production is stimulated by AT-II Production is stimulated by AT-II Physiological action: Physiological action: Reabsorption of sodium, excretion of potassium and hydrogen: Reabsorption of sodium, excretion of potassium and hydrogen: Kidney: Cortical collecting duct Kidney: Cortical collecting duct Sweat, saliva, gastric juice Sweat, saliva, gastric juice

Conn syndrome: Tumor of adrenal cortex, producing excess aldosterone: Tumor of adrenal cortex, producing excess aldosterone: Hypertension Hypertension Hypokalaemia Hypokalaemia Alkalosis Alkalosis

Brain---heart: Sympathetic nervous system: Sympathetic nervous system: Acts on adrenal medulla: Increase catecholamines, increase in stroke volume and heart rate Acts on adrenal medulla: Increase catecholamines, increase in stroke volume and heart rate Acts on kidney: Increase production of renin Acts on kidney: Increase production of renin Other hormones: Growth hormone: Trophic effect on heart Other hormones: Growth hormone: Trophic effect on heart

Endothelium: An organ An organ 2`nd largest organ in body 2`nd largest organ in body Largest=fat Largest=fat Why an organ: It produces hormones Why an organ: It produces hormones Weight of endothelium +/- 1.5 kg Weight of endothelium +/- 1.5 kg Endothelium: 4 groups of functions: Endothelium: 4 groups of functions:

Maintains balance between vasoconstriction and vasodilatation: Maintains balance between vasoconstriction and vasodilatation: NO, bradykinin, ANP: Vasodilatation NO, bradykinin, ANP: Vasodilatation AT-II, thromboxane A2: Vasoconstriction AT-II, thromboxane A2: Vasoconstriction

Maintains balance between thrombosis and fibrinolysis: Maintains balance between thrombosis and fibrinolysis: Tissue factor (factor III): Thrombosis Tissue factor (factor III): Thrombosis T-PA: Tissue type plasminogen activator: Fibrinolysis T-PA: Tissue type plasminogen activator: Fibrinolysis

Maintains balance between inflammation and anti-inflammatory mechanisms. Maintains balance between inflammation and anti-inflammatory mechanisms. Endothelium produces adhesion molecules: ICAM, PECAM, VECAM etc Endothelium produces adhesion molecules: ICAM, PECAM, VECAM etc

Maintains balance between growth and apoptosis: Maintains balance between growth and apoptosis: Angiotensin II: A growth factor, mitogen, causes hypertrophy of arterial intima Angiotensin II: A growth factor, mitogen, causes hypertrophy of arterial intima