Abstract
Background: Salt is an important component for normal function of cells. However, we consume more than 10 times the salt that is required. This high salt content affects the renin–angiotensin–aldosterone system (RAAS) that regulates blood pressure (BP) and water content of our body. Angiotensinogen is an oligopeptide hormone precursor serving as a substrate for renin in the formation of angiotensin I. Angiotensin I is converted to angiotensin II that causes vasoconstriction and a subsequent increase in BP. We hypothesized that angiotensinogen secretions increases in the kidney and urine with intake of high salt diet.
Methods: Dahl salt sensitive (SS) and salt resistant (SR) male rats (8 weeks old) were fed with high salt (HS) and low salt (LS) diet along with or without aldosterone (ALDO); aldosterone antagonist, eplerenone (EPL); and NADPH oxidase inhibitor, apocynin (APC) for 21 days. Urine samples and kidney were collected; total proteins isolated, and quantified using the microassay procedure and analyzed by western blot for angiotensinogen.
Results: Angiotensinogen was detected in the kidney samples of Dahl SS rat when fed either low or high salt diet, whereas angiotensinogen was detected in kidney samples of Dahl SR rats when fed with high salt diets. Angiotensinogen was not detected in urine samples.
Conclusions: In conclusion, consuming a high salt diet increases Angiotensinogen that lead to an increase in angiotensin II which may cause an increase in BP.
Acknowledgements: Vivien Thomas Summer Research Program, Morehouse School of Medicine, Atlanta, GA, USA.
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Hypertensive kidney disease is primarily caused by chronic high blood pressure. Hiranandani Hospital kidney care experts tell us that factors such as a family history of hypertension, unhealthy lifestyle habits, obesity, and certain preexisting medical conditions can aid hypertensive kidney disease development. By understanding the underlying causes, you can take proactive steps to manage your blood pressure and protect your kidney health.
Water and electrolytes especially sodium are closely associated in their regulation in the body. Both are tightly regulated as a tilt of one may result in serious consequences to an individual.
MEANING
Sudden and often temporary loss of kidney function.
DEFINITION
Acute renal failure (ARF) is an abrupt and sudden reduction in renal function resulting in the inability to excrete metabolic wastes and maintain proper fluid & electrolyte balance.
• It usually associated with oliguria (less than 500ml/day), no oliguria (greater than 800ml/day) or anuria (less than 50ml/day).
• BUN &creatinine values are elevated.
Etiology
ARF can be further divided into pre-renal, intra renal and post renal etiologies.
1) Pre- Renal causes
Are those that decrease effective blood flow to the kidney and cause a decrease in the glomerular filtration rate (GFR). Both kidneys need to be affected as one kidney is still more than adequate for normal kidney function.
Volume depletion resulting from:
• Hemorrhage
• Renal losses (diuretics, osmotic diuresis)
• Gastrointestinal losses (vomiting, diarrhea, nasogastric suction)
Impaired cardiac efficiency resulting from:
• Myocardia infraction
• Heart failure
• Dysrhythmias
• Cardiogenic shock
Vasodilation resulting from:
• Sepsis
• Anaphylaxis
• Antihypertensive medications or other medications that cause vasodilation.
2) Intrarenal causes
Refers to disease processes which directly damage the kidney itself. It can be due to one or more of the kidney’s structures including the glomeruli, kidney tubules or the interstitium.
Prolonged renal ischemia resulting from:
• Pigment nephropathy (associated with the breakdown of blood cells containing pigments that in turn occlude kidney structures)
• Myoglobinuria (trauma, crush injuries, burns)
• Hemoglobinreuria (transfusion reaction, hemolytic anemia)
Nephrotoxic agents such as:
• Aminoglycoside antibiotics (gentamycin, tobramycin)
• Radiopaque contrast agents
• Heavy metals (lead, mercury)
• Solvents and chemicals (ethylene glycol, carbon tetrachloride, arsenic)
• NSAIDS
• ACE inhibitors
Infections processes such as:
• Acute pyelonephritis
• Acute glomerulonephritis
3) Post renal causes
Refers to mechanical obstruction of urinary outflow, between the kidney and the urethral meatus, which includes urethral and bladder neck obstruction due to:
Calculi formation
Benign prostatic hyperplasia
Tumors
Strictures
Trauma (to back, pelvis or perineum)
Blood clots
Pathophysiology
The kidneys receive approximately one fourth of cardiac output; therefore, they are very sensitive to alteration in perfusion. Most cases of ARF are caused by ischemia episode. The pathophysiology of ARF is not completely understood.
PrerenalARF, is the result of impaired blood flow that leads to hypo perfusion of the kidney which causes decreased oxygen delivery that leads to hypoxemia and ischemia due to damage the kidney and glomerular filtration rate (GFR) decreases that leads to electrolyte imbalance and increased tubular reabsorption of sodium and water.
Intrarenal ARF is the result of actual parenchymal damage to the glomeruli or kidney
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EFFECTS OF EXCESS SALT DIET ON ANGITENSINOGEN SECRETIONS IN THE KIDNEY OVER TIME
1. EFFECTS OF EXCESS SALT
DIET ON ANGITENSINOGEN
SECRETIONS IN THE KIDNEY
OVER TIME
Chieh-Yin Kuo,
Vivien Thomas Summer Research Program;
Department of Pharmacology & Toxicology,
Morehouse School of Medicine, Atlanta.
2. SALT (SODIUM CHLORIDE, NACL)
INTAKE
• Add flavor to our food.
• Adults need ~6g (or around about a teaspoon) of salt a
day.
• According to the World Health Organization (WHO), the
current global average intake of salt is between 9g and
12g per day or more.
3. KIDNEY
An essential organ in the urinary system
Serve for homeostatic functions
(the regulation of electrolytes, maintenance of acid–base
balance, and regulation of blood pressure via maintaining salt
and water balance)
4. KIDNEY DISEASES
Kidney removes waste products from blood and regulate the
water fluid
High salt diet reduce function and removed less water in the
kidney. This result in high blood pressure (BP) and kidney
disease .
African American are 3-5 times more likely to suffer kidney
failure than Caucasian.
African American with diabetes are 10 times more likely to
have kidney failure.
5. ANGIOTENSINOGEN
Oligopeptide hormone precursor serving as a
substrate for renin in the formation of angiotensin I
Angiotensinogen produced in liver
Causes vasoconstriction and a subsequent increase in
blood pressure.
6. RENIN- ANGIOTENSINOGEN
Renin, which is primarily released by the kidneys, stimulates the
formation of angiotensin in blood and tissues, which in turn
stimulates the release of aldosterone from the adrenal cortex.
Dr Bayorh’s lab has
previously shown that a HS
diet increases Angiotensin II.
My job was to see if HS diet
increases Ang II by
increasing
Angiotensinogen.
7. RENIN- ANGIOTENSINOGEN
Acts on the adrenal cortex to release aldosterone, which in turn
acts on the kidneys to increase sodium and fluid retention
Stimulates the release of vasopressin (antidiuretic hormone,
ADH) from the posterior pituitary, which increases fluid retention
by the kidneys
Stimulates thirst centers within the brain
8. HYPOTHESIS
We hypothesized that angiotensinogen secretion
increases in the kidney and urine with high salt diet.
9. METHODS
Dahl salt sensitive (SS) rat and salt resistance (SR) rats (8 weeks old)
were divided into following groups and treated as mentioned below
for 21 days.
Group 1 : low salt (0.3% NaCl) control
Group 2 : high salt (8% NaCl) diet
Group 3 : low salt diet + aldosterone (ALDO; 0.2 mg pellet)
Group 4 : high diet + aldosterone (ALDO; 0.2 mg pellet)
Group 5 : high diet + apocynin (APC, 1.5 mM in the drinking water)
Group 6 : high diet + Eplerenone (EPL)
Apocynin, is a NADPH oxidase inhibitor; blocks the bad effects of angiotensin II
Eplerenone, is an aldosterone antagonist; blocks the effects of aldosterone
10. METHODS
Microassay Procedure was used to analyzed total protein
content in the urine sample of rats.
13. RESULT
S
Normal rat :
Average systolic pressure = 121 mmHg; Average diastolic pressure = 84 mmHg;
Average mean pressure = 103 mmHg; Heart rate = 380 beats per minute
16. RESULTS-
WESTERN BLOT ANALYSIS ON
ANGINOTENSINOGEN
Additional analysis required to better understand the results above.
17. CONCLUSIONS
These findings suggest that consuming high salt
diets increase Angiotensinogen that leads to an
increase in Angiotensin II which may cause an
increase in blood pressure.
18. Take Home Message
Key messages to protect kidney health
• Become a label reader
• Take every day fresh fruits and vegetables as a major part of diet
• Avoid fast foods and processed food
• Drink more water
19. Future goal
• Increase the number of samples for this
study.
• Also, examine how high salt diet affects
kidney functions.
20. ACKNOWLEDGEMENT
Dr. Danita Eatman
Dr. Mohamed A. Bayorh
Mrs. Aisha Rollins-Hairston
Ms. Nithya Rajendran
Ms Raeonda Williams
Mrs. Wanda Harvey
Vivien Thomas Summer Research Program,
Morehouse School of Medicine, Atlanta.