Lecture 1 Flashcards
How does angiotensin II effect blood pressure
- it is more potent than norepinephrine
- it has little to no effect on bradycardia due to the fact that it effects the brain and not the heart
ANS:
Stimulates autonomic ganglia increases release of epinephrine and norepinephrine from the adrenal medulla
How does angiotensin effect the adrenal cortex and kidneys
Aldosterone synthesis acts on zone glomerulosa
Glucocorticoid synthesis so ag II is higher
Can contribute the cardiovascular hyper trophy
Can caused hypertensive disease
Due to overactivity of renin
Angiotensin II on the CNS
- Central effects on blood pressure
- Stimulates drinking
- Increase secretion of vasopressin and adrenocorticotropic hormone
How is the renin angiotensin system inhibited
Some drugs:
block renin release,
but most:
inhibit the conversion of ANG I to ANG II,
block angiotensin AT 1 receptors, or
inhibit the enzymatic action of renin.
What are some anginotensin converting enzyme inhibitors
Captopril, enalapril, lisinopril, ramipril
How do the anginotensin converting enzyme inhibitors work
Inhibits ACE by constricting the efferent arterioles, so increase renin due to loss of negative feedback and prevents inactivation of bradykinin
Can be used for hypertension
But could cause hypotension, coughing and hyperklalcemia
What causes hereditary angioedema
C1 esterase inhibitor deficiency due to unregulated activation of kallokrenin characfised by low CD4 levels
When are angiotensin II receptor blockers used and what are they
They have a diff mechanism to ACE inhibitors, it is used as a treatment to hypertension to people that can not tolerate ACE inhibitors due to cough or angioedema which is supposed to be mediated by elevated bradykinin levels
They DO NOT INCREASE BRADYKININ
Patients with HF have what
Elevated levels of aldosterone due to angiotensin II stinulation and reduced hepatic clearance of the hormone
What enzyme catalyzes the conversion of angiotensinogen to angiotensin I?
Renin
What is the function of the renin-angiotensin system?
A
A: It regulates fluid and electrolyte balance and arterial blood pressure.
Q: What factors affect renin secretion?
Macula densa, renal baroreceptor, and the sympathetic nervous system.
How does the macula densa regulate renin release?
It signals changes in renin release, with an inverse relationship between NaCl concentration and renin release.
What is the role of angiotensin II in blood pressure regulation?
It is a potent vasoconstrictor that increases blood pressure and promotes aldosterone release.
What are the effects of angiotensin II on the kidney?
A: It causes renal vasoconstriction, increases sodium reabsorption, and inhibits renin release.
Q: What are the primary intracellular messengers controlling renin release?
A: cAMP, cGMP, and intracellular Ca2+ concentration
Name three drugs that stimulate renin releas
Vasodilators (hydralazine), β-adrenoceptor agonists, and phosphodiesterase inhibitors.
Q: What drugs inhibit renin release?
A: Clonidine, propranolol, and other β-blockers.
What is the function of ACE2?
: It converts angiotensin II to angiotensin 1-7, which acts as a vasodilator.
What is the primary function of aldosterone?
A: It promotes sodium retention and potassium excretion in the kidney.
How do ACE inhibitors lower blood pressure?
A: They block the conversion of angiotensin I to angiotensin II and inhibit bradykinin degradation.
Q: What is the mechanism of angiotensin receptor blockers (ARBs)?
A: They block angiotensin II type 1 receptors to reduce vasoconstriction and aldosterone secretion.
What are spironolactatw and epleeenone
Spironolactone and eplerenone are antagonists of aldosterone at the mineralocorticoid receptor, thereby preventing salt retention, myocardial hypertrophy, and hypokalemia.
• Spironolactone also has affinity for androgen and progesterone receptors, and is associated with endocrine-related adverse effects such as gynecomastia and dysmenorrhea.
• Aldosterone antagonists are indicated in patients with symptomatic HFrEF or HFrEF and recent myocardial infarction.
What are natriuretic peptides, and what do they do?
A: They are hormones that promote natriuresis (salt excretion), diuresis, and vasodilation.
What enzyme metabolizes natriuretic peptides?
Neutral endopeptidase.
What is the function of neprilysin inhibitors
?
A: They increase circulating vasoactive peptides by inhibiting neprilysin. It breaks down vasoactive peptides
Why is ARB rather than ACE inhibitors combined with Neprilysin
To reduce incidence of angioedema
Q: What is Sacubitril-Valsartan used for?
A: It treats heart failure by combining an ARB with neprilysin inhibition.
What drugs block the endothelin system?
A: Bosentan, ambrisentan, and sitaxsentan.
Where are some drugs that block the release of renin and how?
Clonidine- by causing a centrally mediated reduction in renal
sympathetic nerve activity, and it may also exert a direct intrarenal action.
• Propranolol and other B-blockers- by blocking the intrarenal and extrarenal
B receptors involved in the neural control of renin release.
What is the role of ACE inhibitors
ACE inhibitors not only block the conversion of ANG I to ANG Il but also
• inhibit the degradation of bradykinin, substance P, and enkephalins. We can have adverse side effects like engioedema and cough
These drugs are contraindicated in pregnancy because they cause fetal kidney damage.
What is the kallikrein kinkn system
Factor XII -> prekalikrein-> Kallikrein->
1) plasminogen to plasmin
2) bradykinin
What is the Kim effect on the cardiovascular system
Kinins produce marked arteriolar dilation in several vascular beds, including the heart, skeletal muscle, kidney, liver, and intestine
What is the kinkn effect on the endocrine and exocrine glands
Prekallikreins and kallikreins are present in several glands, including the pancreas, kidney, intestine, salivary glands, and sweat glands, and they can be released into the secretory fluids of these glands.
Kinkn role in inflammation and pain
Bradykinin produces the four classic symptoms of inflammation-redness, local heat, swelling, and pain.
Kinins are rapidly generated after tissue injury and play a pivotal role in the development and maintenance of these inflammatory processes.
Kinins are potent pain-producing substances when applied to a blister base or injected intradermally.
They elicit pain by stimulating nociceptive afferents in the skin and viscera.
What 2 plasma kinase have been well characterised
Two plasma kininases have been well characterized.
• Kininase I, synthesized in the liver.
• Kininase Il is present in plasma and vascular endothelial cells throughout the body.
What is the role of vasopressin
Vasopressin (AVP/ADH) helps regulate blood pressure in two ways:
1. Long-term regulation – It increases water reabsorption in the kidneys, helping maintain blood volume and pressure.
2. Short-term regulation – It acts as a vasoconstrictor, increasing total peripheral resistance and raising arterial pressure, even at low doses.
What drug is used to treat diabetes inspindus
Desmopressin
ET1
ET-1 is the predominant endothelin secreted by the vascular endothelium. It is also produced by neurons and astrocytes in the central nervous system and in endometrial, renal mesangial, Sertoli, breast epithelial, and other cells.
VIV administration of ET-1 causes a rapid and transient decrease in arterial blood pressure followed by a sustained increase.
ET2
ET-2 is produced predominantly in the kidneys and intestine; ET-3 is found in highest concentration in the brain but is also present in the gi tract, lungs, and kidneys.
Endothelin-1 structure in humans
• Endothelins are present in the blood but in low concentration;
Systemic administration of endothelin receptor antagonists or endothelin-converting enzyme inhibitors causes what
• vasodilation and
• decreases arterial pressure in humans and experimental animals.
What is substance P
Belongs to the tachykinin family (along with neurokinin A & B).
• Functions: Involved in pain perception and chemotherapy-induced nausea & vomiting.
• Vascular effects:
• Potent arteriolar vasodilator, causing hypotension.
• Mediated by nitric oxide (NO) release from endothelium.
• Conversely, causes venous, intestinal, and bronchial smooth muscle contraction.
• Other effects:
• Stimulates salivary gland secretion.
• Causes diuresis and natriuresis in the kidneys.
Vasoactive intestinal peptide
28-amino-acid peptide from the glucagon-secretin family.
• Neurotransmitter in the central and peripheral nervous systems.
• Cardiovascular effects:
• Potent vasodilator (stronger than acetylcholine).
• Coronary vasodilation.
• Positive inotropic & chronotropic effects (enhances heart contraction & rate).
• Regulates coronary blood flow, cardiac contraction, and heart rate.
what are some vasoconstrictors
vasopressin
angiotensin II
Neuropeptride Y
urotensin
endothelials
what are some vasodilators
bradykinin
natriuitic peptides
substance P
neurotensin
cGRP
