Midterm 2 Flashcards
Learn the topics of "Blood Pressure 2", "Vascular Function" and "Reactive Oxygen Species"
Long term mechanisms of blood pressure control depends mostly on _____ function through _____ control
kidney, hormonal
What is the name of the hormone system responsible for controlling kidney function and blood pressure?
Renin-angiotensin-aldosterone system
ADH
antidiuretic hormone (also called arginine vasopressin)
_____ and ____ regulate sodium and water retention affecting blood volume and thereby blood pressure
Aldosterone, ADH
Secretory function of the adrenal gland is regulated by _____ _____ _____ activity and _____ factors
sympathetic nervous system, humoral
Adrenal gland is important in the secretion of:
Cortisol- energy metabolism
Epinephrine- stress, exercise
Aldosterone- blood volume, blood pressure regulation
Which part of the nephron contains baroreceptors?
Afferent arteriole
The functional unit of the kidney
Nephron
Approximately how many nephrons are in a singular kidney?
1.5 million
Branched high pressure capillaries located in the Bowman’s capsule
Glomerulus
The high pressure in the glomerulus…
forces things (H2O, Na+, glucose) out of the blood
Exits the glomerulus and forms new capillaries that wrap around the PCT, Loop of Henle, and DCT
Efferent arteriole
PCT
Proximal convoluted tubule
DCT
Distal convolutes tubule
Ions, water, vitamins, glucose are reabsorbed in which areas of the nephron?
Proximal convoluted tubule, Loop of Henle, distal convoluted tubule, and the collecting duct
If H2O filtration rate (GFR) > H2O reabsorption then…
Urine output increases, blood volume decreases, blood pressure decreases
Decreased VR = Decreased CVP = Decreased EDV/ESV = Decreased MAP
Macula densa
Specialized cells lining the wall of the distal convoluted tubule that monitor flow through the distal convoluted tubule and the concentration of sodium ions
Regulates the release of renin from the juxtaglomerular cells
Macula densa
What hormone does the liver constitutively secrete into the blood?
Angiotensinogen
What is the rate limiting enzyme in the renin-angiotensin-aldosterone system (RAAS)?
Renin- it is required to cleave angiotensinogen to form Angiotensin I
How is Angiotensin I converted to Angiotensin II?
Angiotensin converting enzyme (ACE)
Endothelial cells contain _____ _____ _____; primarily the lungs
Angiotensin converting enzyme (ACE)
Angiotensin II interacts with what four structures?
Arterioles and veins, the adrenal cortex,collecting ducts in the kidney, and the posterior pituitary gland
True or false: Ag II induces vasoconstriction via vascular smooth muscle cells
True
Angiotensin II binds to _____ _____ _____ Receptors on the vascular smooth muscle cells, _____ _____ _____ receptors belong to the Gq protein coupled receptor family and act through the _____ _____ ______ pathway and _____ _____ pathway
Angiotensin Type 1 (AT1), angiotensin type I (AT1), phospholipase C-inositol triphosphate (IP3), rho kinase
Increased Angiotensin II stimulates the secretion of _____ from the _____ _____ to the blood
aldosterone, adrenal cortex
Aldosterone increases the rate of _____ reabsorption in the _____ _____ ______ and collecting duct
sodium (Na+), distal convoluted tubule
Aldosterone also increases the rate of _____ reabsorption by the direct activation of Na+/H+ exchangers and Na+ channels
sodium (Na+)
Increased reabsorption of _____ leads to increased reabsorption of _____ and thus increases venous return and mean arterial pressure
sodium (Na+), water (H2O)
Angiotensin II stimulates the secretion of _____ _____ from the _____ pituitary gland
antidiuretic hormone, posterior
Diuretic
Increases urine output
How does antidiuretic hormone regulate blood pressure?
It moves aquaporins to the apical surface of the plasma membrane in order to increase water reabsorption and therefore increase blood volume
What class of hormones opposes the renin-angiotensin-aldosterone system?
Natriuretic hormones (e.g. arterial natriuretic peptide, ANP, which is released from the atria in response to stretching in the atrial walls)
Arterial natriuretic peptide acts by inhibiting the secretion of _____ from the adrenal cortex
aldosterone
Inhibition of aldosterone secretion leads to…
less sodium (Na+) reabsorption and therefore less water reabsorption
Arterial natriuretic peptide acts by inhibiting the secretion of _____ from the posterior pituitary gland
antidiuretic hormone (ADH)
Arterial natriuretic peptide acts on the vascular _____ _____ of veins and arterioles by increasing the concentration of _____
smooth muscle, cGMP (results in venodilation and vasoconstriction)
Arterial natriuretic peptide acts by inhibiting the secretion of _____ from the juxtaglomerular cells
renin (reduces Ag II)
What is a reactive oxygen species (ROS)?
Highly reactive compounds formed in every cell. There is a basal level of ROS production at rest which can increase in times of stress. They contain at least one O2 (ROS) or one nitrogen (NOS).
What is a free radical?
These compounds fall under the ROS category and contain at least one unpaired electron (e.g. O2-, superoxide)
NOX
NADPH oxidase- a protein complex that produces primarily superoxide. NADPH + O2 –(NOX)–> NADP+ + H+ + O2-
eNOS
Endothelial nitric oxide synthase- a transmembrane protein that produces nitric oxide from L-arginine
ONOO-
Peroxynitrite- a ROS formed from superoxide and nitric oxide
Complex I, II, III and PMF all have the potential to form _____
superoxide
Enzymatic antioxidants
Superoxide Dismutase (MnSOD or CuZnSOD) and catalase
Non-enzymatic antioxidants
alpha-tocopherol (vitamin E), ascorbate (vitamin C), retinol (vitamin A), and glutathione (GSH)
ROS-mediated _____-_____ modifications of proteins is an important means of controlling protein _____
post- translational
ROS affects the _____ _____ of a protein which will alter the activity for better or for worse
3D structure
A protein with two thiol groups can form sulfenic acid by the addition of _____ _____
hydrogen peroxide
Sulfenic acid can form an intramolecular disulfide bond, an intermolecular disulfide bond, s-glutathiolation or sulfinic acid
Intramolecular disulfide bond- water dehydrates
Intermolecular disulfide bond- another molecule with a thiol group interacts with R-SOH group
Sulfinic acid- hydrogen peroxide interacts with the R-SOH group (R-O2H formed)
S-glutathiolation- glutathione adds SH and removes OH to form water
Optimal ROS production occurs during…
moderate stress like exercise
Oxidative stress
ROS production too great
In S1 hypertension systolic BP = _____ and diastolic BP = _____
130-139, 80-89
In S2 hypertension systolic BP = _____ and diastolic BP = _____
> 140, >90
Primary hypertension
- also known as essential hypertension or idiopathic hypertension
- bp increases without identifiable cause
- most common (>95% of cases)
- contributing factors are genetic, environmental and behavioural
Secondary hypertension
- elevated bp with an unidentifiable cause
- usually renal, endocrine or drugs treating other diseases/conditions
Why does the probability of developing hypertension increase as we age>
Due to stiffening of the large arteries
______ are more likely to develop hypertension before the age of 55
Men
The intersalt study looked at _____ and found a relationship between developing it and _____ consumption
hypertension, salt
Hypertension due to increased salt consumption is the result of…
vasoconstriction due to increased Ca2+ due to activation of NCX (sodium-calcium exchanger) Ca2+ binding CM (calmodulin) and then Ca-CM (calcium-calmodulin) binding MLCK (myosin light-chain kinase)
What consequences are there for a reduction in eNOS activity?
A decrease in nitric oxide production; decreased nitric oxide bioavailability. Nitric oxide is unable to activate guanylate cyclase which results in a decrease in cGMP and MLCP (myosin light-chain phosphatase) activity (i.e. VSMC tone increases)
Renal artery stenosis
Narrowing of one of the renal arteries, most often caused by atherosclerosis or fibromuscular dysplasia.
Renovascular disease
A progressive condition that causes narrowing or blockage of the renal arteries or veins.
_____ plaque can form in the renal artery or smaller arteries from the renal artery
Atherosclerotic
Creation of a _____ in the artery is the result of a build up atherosclerotic plaque
stenosis
Downstream of a stenosis you would expect…
a substantial drop in blood pressure
Why is there such a drop in blood pressure following a stenosis?
Vasodilation occurs in an attempt to maintain adequate blood flow
In renal artery stenosis, a drop in blood pressure will be observed in the _____ _____ just downstream the renal artery and lead to low blood pressure being detected by the _____ _____ ______ and causing increased SNS activity to the juxtaglomerular cells and ultimately _____ release
afferent arteriole, afferent arteriole baroreceptors
List the steps in renal artery stenosis
atherosclerotic plaque forms stenosis in renal artery, downstream bp is reduced, afferent arteriole baroreceptors activate SNS response to juxtaglomerular cells, juxtaglomerular cells release renin, renin cleaves angiotensinogen to form angiotensin I, angiotensin I is converted to angiotensin II by angiotensin converting enzyme
List the effects in order of angiotensin II interacting with vascular smooth muscle
Angiotensin II binds angiotensin type 1 Gi coupled receptor, decrease in adenylate cyclase activity, decrease in cAMP concentration, decrease in protein kinase A activity, increased myosin light-chain kinase activity, and thus increased tension
C57/BL6 is a genetically _____ mouse for the p47phox
normal
p47phox-/- is has a gene for a subunit of _____ _____ knocked out
NADPH oxidase
p47phox-/- mice had…
a) higher superoxide production than C57/BL6 mice
b) lower superoxide production than C57/BL6 mice
c) identical superoxide production to C57/BL6 mice
b)
What class of diuretics is typically used in the initial stages of treating hypertension?
Thiazides
A chemical inhibiter of the Na+/Cl- symporter of the distal convoluted tubule of the nephron
Hydrochlorothiazide
What are the two classes of renin-angiotensin-aldosterone system (RAAS) inhibiting drugs?
Angiotensin converting enzyme (ACE) inhibitors, and angiotensin type 1 receptor (AT1R) blockers
AT1 Receptor Blockers work by…
preventing angiotensin II from binding to AT1 receptors, reducing intracellular signalling and preventing the depletion of NO bioactivity
Beta Blockers
B-adrenergic receptor blockers- blocks norepinephrine (NE) from binding to B-adrenergic receptors
What effect do beta blockers have on the circulatory system?
Decrease inotropy = increase in end-systolic volume = decrease stroke volume = decrease in cardiac output = decrease in systolic blood pressure = decrease in mean arterial pressure
What effect do beta blockers have when they bind the B-adrenergic receptors of the sinoatrial node?
Decreased heart rate = decreased cardiac output = decrease in systolic blood pressure = decrease in mean arterial pressure
In Ca2+ channel blockers what two channels are targeted?
Dihydropyridine receptors (DHPRs), and L-type channels
What effect does decreased Ca2+ entry into the cell during depolarization have?
Ventricular cardiomyocytes: decreased inotropy in left ventricle (increased end-systolic volume = decreased stroke volume = decreased cardiac output)
Sinoatrial nodal cells: negative chronotropic effect (decreases heart rate)
What effect does a Ca2+ channel blocker (CCB) have on vascular smooth muscle?
Decreases calcium entry = decreases Ca-CM = decreases MLCK activity
Results in vasodilation, thus decrease in TPR (MAP = CO X TPR)
