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Submitted By-
Navneet kaur
B PHARM 4TH YEAR
Supervisor –Supandeep singh
hallan
Jaskamal singh gill 1
HYPERTENSION
Hypertension (HTN or HT), also known as high
blood pressure (HBP), is a long term medical
condition in which the blood pressure in the arteries is
persistently elevated. High blood pressure usually does
not cause symptoms. Long term high blood pressure,
however, is a major risk factor for coronary artery
disease, stroke, heart failure, peripheral vascular
disease , vision loss, and chronic kidney disease.
2
TYPES OF HYPERTENSION
 Essential hypertension. Usually people with essential
hypertension have no symptoms, but you may experience
frequent headaches, tiredness, dizziness, or nose bleeds.
Although the cause is unknown, obesity, smoking,
alcohol, diet and heredity all play a role in essential
hypertension.
 Secondary hypertension. The most common cause of
secondary hypertension is an abnormality in the arteries
supplying blood to the kidneys. Other causes include airway
obstruction during sleep, diseases and tumors of the adrenal
glands, hormone abnormalities, thyroid disease, and too
much salt or alcohol in the diet.
3
Blood Pressure Classification
Normal <120 and <80
Prehypertension 120–139 or 80–89
Stage 1
Hypertension
140–159 or 90–99
Stage 2
Hypertension
>160 or >100
BP
Classification
SBP
mmHg
DBP
mmHg
4
ISCHEMIA
Ischemia is a restriction in blood supply to tissues,
causing a shortage of oxygen and glucose needed for
cellular metabolism (keep tissue alive). Ischemia is
generally caused by problems with blood vessels, with
resultant damage to or dysfunction of tissue. It also
means local anemia in a given part of a body sometimes
resulting from congestion (such as vasoconstriction,
thrombosis or embolism).
5
ISCHEMIA-REPERFUSION
Reperfusion (reoxygenation) injury is the tissue
damage caused when blood supply returns to the tissue
after a period of ischemia or lack of oxygen (anoxia,
hypoxia). The absence of oxygen and nutrients from blood
during the ischemic period creates a condition in which
the restoration of circulation results
in inflammation and oxidative damage through the
induction of oxidative stress rather than restoration of
normal function.
6
•I/ R INJURY
Ischemia
(inadequate oxygen
supply)
Reperfusion
inflammatory
responses
local injury &
impairment
of organ
function
7
MECHANISM
8
CONDITIONS UNDER WHICH I/R
INJURY IS ENCOUNTERED INCLUDE
• Stroke
• MI
• Organ transplantation
• Cardiopulmonary bypass
9
CELLULAR CHANGE DURING
ISCHEMIA
 Mitochondrial permeability transition (mPT)
• Altered membrane potential
• Altered ion distribution (++ intracellular
Ca/Na)
• Cellular swelling Increased hypoxanthine
• Decreased ATP
• Decreased phosphocreatinine
• Cellular acidosis
10
Therapeutic Interventions Targeting
I/R Injury
Anti-inflammatory
1. Inhibition of leukocyte accumulation
2. Complement inhibition (pexelizumab)
Inhibition of mPTP ( ex: cyclosporine)
Prevention of intracellular calcium
overload
Reducing ROS by Inhibition of xanthine
oxidase
11
PRECONDITIONING
Ischemic preconditioning (IPC) is an experimental
technique for producing resistance to the loss
of blood supply, and thus oxygen, to tissues of many
type In the heart. The local action of adenosine,
opiates and bradykinin which are
all endogenously released by ischemic cells. They
activate G-protein coupled pathways, which carries a
protective signal to an end-effector.
I R I R I R I R
10’S 5’ 5’ 5’ 5’ 5’ 5’ 5’ 5’ 30’I 120’R
12
Material and Methods
Experimental Animals : Sprague Dawley Rats
(200-300g)
Feeding : Chow Diet
Temperature : 20-25℃
Experimental Groups :
i) Normal Control group
ii) DOCA salt administered group
(Desoxycorticosterone Acetate)
13
Mechanism Of Doca Salt
 It acts as a precursor to aldosterone Increased
concentrations of aldosterone lead to increased
reabsorption of sodium ions and water from
epithelial cells in the distal nephron of the kidney
thereby influencing blood pressure levels
 endothelin-1 (peptide) concentrations were
elevated in the DOCA-salt rat, which induced
vasoconstriction
14
Male Sprague Dawley rats weighing 250-300g will be
anesthetized with thiopentone sodium (45mg/kg).
Through a flank incision the left kidney will be removed.
The rats will be injected twice weekly with 20mg/kg S.C
DOCA salt in olive oil for 6 weeks.
Drinking water will be replaced with 1% NaCl solution.
Blood pressure will start to rise after one week and
carried until Mean artrial blood Pressure reaches 110
mmHG.
PROCEDURE
15
PARAMETERS
 LVEDP (Left ventricular end diastolic pressure)
 CK –MB (Creatine kinase )
 HEART RATE AND BP
 MEAN ARTERIAL PRESSURE
 SERUM NITRITE / NITRATE LEVEL (using
Greiss reagent)
16
THANK YOU
17

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pharmacology project

  • 1. Submitted By- Navneet kaur B PHARM 4TH YEAR Supervisor –Supandeep singh hallan Jaskamal singh gill 1
  • 2. HYPERTENSION Hypertension (HTN or HT), also known as high blood pressure (HBP), is a long term medical condition in which the blood pressure in the arteries is persistently elevated. High blood pressure usually does not cause symptoms. Long term high blood pressure, however, is a major risk factor for coronary artery disease, stroke, heart failure, peripheral vascular disease , vision loss, and chronic kidney disease. 2
  • 3. TYPES OF HYPERTENSION  Essential hypertension. Usually people with essential hypertension have no symptoms, but you may experience frequent headaches, tiredness, dizziness, or nose bleeds. Although the cause is unknown, obesity, smoking, alcohol, diet and heredity all play a role in essential hypertension.  Secondary hypertension. The most common cause of secondary hypertension is an abnormality in the arteries supplying blood to the kidneys. Other causes include airway obstruction during sleep, diseases and tumors of the adrenal glands, hormone abnormalities, thyroid disease, and too much salt or alcohol in the diet. 3
  • 4. Blood Pressure Classification Normal <120 and <80 Prehypertension 120–139 or 80–89 Stage 1 Hypertension 140–159 or 90–99 Stage 2 Hypertension >160 or >100 BP Classification SBP mmHg DBP mmHg 4
  • 5. ISCHEMIA Ischemia is a restriction in blood supply to tissues, causing a shortage of oxygen and glucose needed for cellular metabolism (keep tissue alive). Ischemia is generally caused by problems with blood vessels, with resultant damage to or dysfunction of tissue. It also means local anemia in a given part of a body sometimes resulting from congestion (such as vasoconstriction, thrombosis or embolism). 5
  • 6. ISCHEMIA-REPERFUSION Reperfusion (reoxygenation) injury is the tissue damage caused when blood supply returns to the tissue after a period of ischemia or lack of oxygen (anoxia, hypoxia). The absence of oxygen and nutrients from blood during the ischemic period creates a condition in which the restoration of circulation results in inflammation and oxidative damage through the induction of oxidative stress rather than restoration of normal function. 6
  • 7. •I/ R INJURY Ischemia (inadequate oxygen supply) Reperfusion inflammatory responses local injury & impairment of organ function 7
  • 9. CONDITIONS UNDER WHICH I/R INJURY IS ENCOUNTERED INCLUDE • Stroke • MI • Organ transplantation • Cardiopulmonary bypass 9
  • 10. CELLULAR CHANGE DURING ISCHEMIA  Mitochondrial permeability transition (mPT) • Altered membrane potential • Altered ion distribution (++ intracellular Ca/Na) • Cellular swelling Increased hypoxanthine • Decreased ATP • Decreased phosphocreatinine • Cellular acidosis 10
  • 11. Therapeutic Interventions Targeting I/R Injury Anti-inflammatory 1. Inhibition of leukocyte accumulation 2. Complement inhibition (pexelizumab) Inhibition of mPTP ( ex: cyclosporine) Prevention of intracellular calcium overload Reducing ROS by Inhibition of xanthine oxidase 11
  • 12. PRECONDITIONING Ischemic preconditioning (IPC) is an experimental technique for producing resistance to the loss of blood supply, and thus oxygen, to tissues of many type In the heart. The local action of adenosine, opiates and bradykinin which are all endogenously released by ischemic cells. They activate G-protein coupled pathways, which carries a protective signal to an end-effector. I R I R I R I R 10’S 5’ 5’ 5’ 5’ 5’ 5’ 5’ 5’ 30’I 120’R 12
  • 13. Material and Methods Experimental Animals : Sprague Dawley Rats (200-300g) Feeding : Chow Diet Temperature : 20-25℃ Experimental Groups : i) Normal Control group ii) DOCA salt administered group (Desoxycorticosterone Acetate) 13
  • 14. Mechanism Of Doca Salt  It acts as a precursor to aldosterone Increased concentrations of aldosterone lead to increased reabsorption of sodium ions and water from epithelial cells in the distal nephron of the kidney thereby influencing blood pressure levels  endothelin-1 (peptide) concentrations were elevated in the DOCA-salt rat, which induced vasoconstriction 14
  • 15. Male Sprague Dawley rats weighing 250-300g will be anesthetized with thiopentone sodium (45mg/kg). Through a flank incision the left kidney will be removed. The rats will be injected twice weekly with 20mg/kg S.C DOCA salt in olive oil for 6 weeks. Drinking water will be replaced with 1% NaCl solution. Blood pressure will start to rise after one week and carried until Mean artrial blood Pressure reaches 110 mmHG. PROCEDURE 15
  • 16. PARAMETERS  LVEDP (Left ventricular end diastolic pressure)  CK –MB (Creatine kinase )  HEART RATE AND BP  MEAN ARTERIAL PRESSURE  SERUM NITRITE / NITRATE LEVEL (using Greiss reagent) 16