W24 Hypertension 2 Flashcards
what two mechanisms can occur in the structure of resistance arteries
endothelium releases vasodilators
innervated by sympathetic nerves: noradrenaline acts on a1 receptors as the VSM contracts
Describe how the contraction of a smooth muscle cell works
smooth muscle cell made up of thick filaments of myosin and thin actin filaments
dense bodies are cytoplasmic anchorage points.
thick and thin filaments slide over each other during contraction. leading to cross bridge cycling and leads to the shortening of the fibres
describe the mechanism how contraction of vascular smooth muscle work
agonist e.g. noradrenaline binds to a g coupled protein receptor gaq on the vascular smooth muscle cell releasing IP3
this then binds to the IP3 receptor releasing calcium from the sarcoplasmic reticulum
released calcium binds to calmodium
leads to an increase in polarization opening voltage gated calcium channel which leads to calcium moving down the concentration gradient into the vascular smooth muscle cell binding to calmodulin also
calmodulin activates myosin light chain kinase (enzymes)
that then phosphorlyates the myosin light chain
the phosphorylation then initiates constriction
how does endothelial dependant relaxation work
agonist binds to endothelium
leading to increase in calcium which produces nitric oxide and relaxing factor
release of nitric oxide + relaxing factor
decrease calcium in vascular cell as they are absorbed
leading to smooth muscle relaxing
what do increases in EC [Ca2+] activate
nitric oxide synthase COX and EDHF
what happens to nitric oxide after produced in response to calcium increase
diffuses to SMC and activates soluble guanylate cyclase generating cGMP
what does cGMP evoke
relaxation by activating protein kinase G which prevents Ca2+ release and Ca 2+ entry while also regulating Myosin light chain kinase to evoke relaxation
what is PGI2 come from
COX
where does PGI2 diffuse to
SMC activates IP receptor
what does IP receptor do
coupled to AC - cAMP generated activates PKA
what does PKA do
regulates MLCK and activates some SMC K+ channels
what drugs can be used for antihypertension
ACE inhibitors
AT - 1 receptor antagonists
Calcium channel blockers
Potassium channel openers
a 1 adrenoceptor blockers
d1 dopamine agonists
how do calcium channel blockers stop constriction
they block the calcium channel that would be opened as a result of the release of Ca2+ from the sarcoplasmic reticulum
what is the role of calcium channel blockers
block L type VGCC
what are the 3 types of Calcium Channel Blockers
Dihydropyridines - Vascular
Phenethylalkylamines - Cardiac
Benzothiazepines - Mixed
what are 3 examples of dihydropyridines
amlodopine felopine lacidipine verapamil diltiazem
what is an example of phenethylaklylamines
verapamil
what is an example of benzothiazepines
diltiazem
what are the side effects of calcium channel blocker
ankle swelling flushing palpitations tremor constipation hypotension cardiac effects av block weaken heart beat nifedipine increase
what do potassium openers do
hyperpolarization as K+ moves out lessening the concentration gradient meaning less calcium moves in so calmodulin cascade cant occur
what do adrenoceptor antagonist do
prevent the release of IP3 so no release of Ca2+
what system has a profound effect on blood pressure
total peripheral resistance has a profound effect on blood pressure
most antihypertensives agents act directly on the resistance vasculature
what does hypertension tend to cause
tachycardia
what is tachycardia
Heart rate over 100 beats a minute
what system is useful in regulating blood pressure
renal
what two systems regulate each other
sympathetic nervous system + renal system can regulate each other
What do diuretics do
increase volume of urin and water loss
what antihypertensive drugs act on the renal system
Diuretics Ace inhibs AT - 1 receptor inhibitors Beta adrenoreceptor antagonists D1 Dopamine agonists Rennin inhibitors
where is renin released from
juxtaglomerular cells of kidney
what is renin release stimmed by
renin release is stimulated by many drugs including vasodilators, diuretics
what does renin stimulate
conversion of angiotensinogen into angiotensin1
what does angiotensin converting enzyme convert
angiotensin I to angiotensin II
what does angiotensin II activates AT 1 receptor resulting in
vascular smooth muscle cell constriction and increasing blood pressure
increases release of aldosterone
describe how the renin angiotensin + aldesterone works
low sodium in distal tubule,
macula densa
Juxtaglomerular cells
releases renin leading to a lower blood pressure and blood volume. As well as an increase in sympathetic NS beta adrenoceptor.
Renin converts angiotensinogen to angiotensin 1, Ace converts angiotensin 1 to angiotensin 2.
This leads to constriction by the AT1 receptor.
It also leads to an increased secretion of aldosterone which leads to an increased sodium reabsorption by distal tubule.
Give some Ace inhbitors
Ramipril enalapril lisinopril imadapril fosinopril perindopril quinapril trandopril
what do ACE inhibtors do
prevent conversion of angiotensin 1 to angiotensin 2
what are the main side effects of ace inhibitor
cough rash hypotension
what is ace inhibitors contra indicated with
in pregnancy and with NSAID treatment
what is the mechanism of action for ramipril
inhibition of ace
what are three examples of angiotensin 2 receptor antagonists
candesartan olmesartan valsartan
what to angiotensin 2 receptor antagonists
block action of angiotensin 2 on AT1 receptor
what do thiazide like diuretics do
effective antihypertensive weak diuretics
act on the Na/Cl symporter of covuluted distal tubule
give 3 example of thiazide like diuretics
bendroflumethiazide hydrochlorothiazide indapamide chlortalidone metolazone
what are the side effects of thiazide like diuretics
hypokalaemia and metabolic alkalosis
