THE ROLE OF RENAL IN BLOOD PRESSURE REGULATION AND HYPERTENSION

Umar Zein Medical Faculty Prima Indonesia University

Renal Function: Excretory Regulatory Endocrine

Excretory Function: Metabolic Glomerular Glomerular Filtration Rate (GFR) Creatinin Clearance. UxV/P ml/min

Complications of HTN
CNS

Cardiac

Stroke or TIA

Renal

Sequelae of Hypertension
Heart diseases Nephropathy, Proteinuria, CrCl

Retinal

Vascular

Retinopathy

Peripheral arterial Disease (atherosclerotic plaque iliac,carotid, femoral artery, aorta)

Patho-physiology of Hypertension
HTN develop gradually over a long period of time. The development of HTN requires the adjustment of several compensatory mechanisms over time. Several hypothesis exists for the original pathogenesis of HTN:
Excess Na intake Renal Na retention Renal Angiotensin System (RAS) Stress & sympathetic over activity Peripheral resistance cell membrane and endothelial dysfunction Obesity insulin resistance

Regulation of aldosterone secretion

Components of reninangiotensinaldosterone system

Action of aldosterone on the renal tubule.

Excess Na intake
Renal Na retention

Reduced Nephron Numbers

Decreased filtration surface

Stress
Sympatheic Over activity

Genetic Alterations
RAS Excess

Obesity
Cell-membrane alterations

Endothelium derived factors

Hyper insulinemia

Fluid Volume

Venous constriction

Preload

Contractibility

Functional constriction X Peripheral Resistance and/or

Structural hypertrophy

Blood pressure= HTN

Cardiac Output

Pathophysiology of blood pressure changes

BLOOD PRESSURE
CARDIAC OUTPUT
BLOOD VOLUME

PERIPHERAL RESISTANCE
FUNCTIONAL VASOCONSTRICTION

CONTRACTILITY
Normal PULSE RATE Remodeling

STRUCTURAL HYPERTROPHY

Pressure-natriuresis Relation in Arterial Hypertension

Natriuresis

Normotensives

Hypertensives

Guyton, 1972

Blood pressure

Neurohumoral Control of the Cardiovascular System

RAAS
Aldostero ne
Angiotensinogen

SNS

NEP
Natriure sis

Angiotensin I

ACE

ANP

AT II

relaxation Myocardial hypertroph y fbrosis Cardiovascular System

constricti on

Activity of the Autonomic Nervous System in Hypertension

Heart Vessels Pulse rate contractility vasoconstriction Increased resistance Smooth muscle cells membrane activity

Kidney

Sodium retention

Renin-Angiotensin System
The Damaging Effects of Angiotensin II

Renin-Angiotensin System
Angiotensinogen Renin Angiotensin I Bradykinin

tPA Catepsin

B1-R

Chymase

ACE

B2-R

Angiotensin II

Inactive quinines

AT1-R

AT2-R

DIFFERENTIAL EFFECTS OF ANGIOTENSIN RECEPTORS

ANG II

A-II

ANG II

AT1
Vasoconstriction Cell Growth Cell Proliferation Anti-Natriuresis
Production:aldosterone, endothelin, catecholamines, PAI-1 adhesion molecules, growth factors

AT2
Vasodilation? Inhibition of Cell Growth Cell Differentiation Apoptosis Natruiresis
Production :Nitric Oxide

Effects of angiotensin II
Water and sodium retention
Peripheral vasoconstriction Renin secretion

Vascular proliferation

AII AT1-R

Aldosterone secretion

Adrenergic
activity Efferent arteriole vasoconstriction

Thirst mechanism

Bradykinin and Endothelins

Proendothelins Bradykinin
ET1 ET2 ET3

B1-R

B2-R ETB-R ETA-R

Endothelial Cell Smooth Muscle Cell

Nitric Oxide
vasodilatation Vasoconstriction

Nitric Oxide (NO)

L-arginine
eNOS oxidases

NO
cGMP Nitrogenated Heam-proteins Renin Secretion

O 2-

Peripheral
vasoconstriction

Renal
resistance

NO

Sodium
Reabsorption Pressurenatriuresis

Glomerulo-tubular
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