sodium therapy

3. • Presence of a tissue based RAS in the vasculature
• The functional capacity of RAS was previously
unknown
• Investigation took place
• To find out the effects of sodium at different levels
• 28 normotensive people were required
• The amount of production of Ang I and Ang II
• Location: Vascular beds(forearm and leg)

4. RAS
(Renin-Angiotensin System)
• Hormonal system
• Regulates blood pressure and fluid balance
• If RAS is abnormally active then blood pressure will be too
high

5. Kidneys convert prorenin to renin
Directly secreted into the circulation
Renin converts Angiotensinogen to Ang I
Ang I is converted to Ang II by ACE
Ang II causesStimulates secretion of
aldosteron from adrenal cortex
Constriction of
vessels
Reabsorption of Na and water
Increases volume of extracellular fluid
Increases blood pressure
Renal blood flow reduced in the kidneys

6. • Presence of intrinsic RAS in different tissues and organs
• RAS divided into two: LOCAL and FETAL
• Local RAS was discovered by isolation of organs from rats and
dogs
• Major role: Production of Ang I and Ang II
• Elements of RAS
renin angiotensin Angiotensin
receptors
Angiotensin
converting
enzyme (ACE)

7. • RAS can play a major role in these diseases
 Hypertension
 Artherosclerosis
 Heart failure
• Ang II has multiple vascular functions:
 Vasoconstrictor effect
 Enhancement of sympathetic adrenergic transmission
 Myogenic and trophic actions in the vasculature
• HYPOTHESIS: “RAS EXISTS IN THE VASCULATURE”
 Found out level of Ang I and Ang II in the vascular beds
 Kinetics of radiolabelled Angiotensins

8. Methods

9. Subjects Investigated
• 28 Normotensive subjects(19 men and
9 women)
• Age 25-43
• No medication used for 15 days before
the test
• Blood glucose, Hematocrit, and
cholesterol should be normal

10. Study Design
• Ang I and II were measured in peripheral and venous blood of
the forearm
• Blood from femoral vein was drawn to check production and
kinetics in leg vascular bed
• PRA was assayed in peripheral venous blood
• Investigation began after a week of normal Na diet
• Subjects divided into two groups
I-Ang I kinetics in 14 patients
Group A Group B
7 low Na 7 high Na
I Ang II kinetics in 14 patients
7 low Na 7 high Na

11. • Subjects for leg investigation were also divided into groups
I-Ang I kinetics in 10 people I Ang II kinetics in 10 people
5 low Na 5 high Na 5 low Na 5 high Na
•During the three diet period all subjects had the same diet
•Only the amount of sodium varied

12. Experimental Procedure
• Test performed in the morning(over-night fasting)
• Local anesthesia given before
• Collection of samples was done by cannulating the:
 Left brachial Artery- arterial samples
 Left anticubital vein- venous samples
 Femoral vein- blood sample of leg
• Right articubital vein cannulated for infusion of I-Ang I and I-
Ang II
• After infusion, initially level of both was high till 15 minutes
• Samples for Ang I and II were collected during this time

13. Assay of Ang I and Ang II
• Blood for assay was collected, centrifuged and stored
• Blood for PRA was collected, centrifuged and stored
• Ang I and II were extracted from plasma and separated by
HPLC
• Elution was performed and eluate collected into tubes
• It was then evaporated in the concentrator
• Now Ang I and Ang II were completely separated
• Similar method separated I-Ang I and I-Ang II

14. Statistical analysis
• T-test: to measure the metabolism of Ang I and II during
different levels of sodium
• ANOVA: To find out differences in parameters of I-Ang I and I-
Ang II kinetics during different levels of sodium

15. Results

16. Angiotensin Formation With Normal Na intake
• Group A and B were given normal sodium diet
• PRA(plasma renin angiotensin)= 10.5pmol/L min
• Concentration in arterial-venous gradient of:
 Ang I= 1.8pmol/L
 Ang II= 0.8pmol/L
• Ang I and II concentrations in patients of group A and B were
similar
• Conversion of I-Ang I I-Ang II in forearm= 12%
 I-Ang I that was extracted= 35.7% (Group A)
 I-Ang II that was extracted= 29.7% (Group B)
• Ang I produced by forearm= 5.1pmol/L
• Ang II produced by by forearm= 6.2pmol/L

17. Angiotensin Formation With Low Na Intake
• Group A and B were given low sodium diet
• PRA increased from 10 to 46.6pmol/L min
• Concentration in blood increased:
 Ang I: 25.1pmol/L 19.3pmol/L
 Ang II: 17.3pmol/L 11.8pmol/L
• Conversion of I-Ang I I-Ang II in forearm= 6%
 I-Ang I that was extracted= 33%
 I-Ang II that was extracted= 29.7%
• Amount of formation of Ang I and Ang II was undetectable
No change in
blood pressure
Forearm blood
flow decreased
Forearm vascular
resistance increased

18. Angiotensin Formation With High Na Intake
• Group A and B were given high sodium diet
• PRA decreased from 10.5 to 7.2pmol/L min
• Concentration in blood:
 Ang I: 1.7pmol/L 3.7pmol/L
 Ang II: 1pmol/L 4.6pmol/L
• I-Ang I and I-Ang II vascular extraction was increased
• Ang I produced: 7.8pmol/L
• Ang II produced: 3.9pmol/L
Blood pressure did not
change significantly
Vascular resistance
decreased