Vascular smooth muscle Flashcards
List the major classes of antihypertension drugs
- Diuretics
- Adrenoceptor antagonist
- Angiotensin converting enzyme inhibitors
- Angiotensin receptor antagonist
- Calcium channel blockers
Hypertensin
High blood pressure
Activation of the sympathetic nervous system and the renin-angiotensin system releases what?
Vasocontrictor hormones: adrenaline, noradrenaline and angiotensin(ii)
What does adrenaline, noradrenaline and angiotensin(ii) activate?
Specific receptors that increase intracellular [Ca2+] that causes vascular SM contraction.
What is the use of Rho kinase and protein kinase C in hormone induced vascular smooth muscle?
Will cause the contraction of SM to be sustained at low Ca2+ levels.
What two things prolong the hormone induced SM contraction
Rho kinase and protein kinase C
‘vasodilators’ are antihypertensive drugs
True
What do antihypertensive drugs do?
Increase the diameter of blood vessels (relax) and reduce vascular resistence & blood pressure.
Antihypertensives that increase the diameter of blood directly.
- Beta-adrenoceptor agonist
- Nitric oxide donors
- Nitric oxide gereators
- K+ channel openers
- Phosphodiesterase inhibitors
- guanylate cyclase stimulators
ANtihypertensive drugs that increase BV diameter by inhibiting endogensous vc substanes.
- ACE inhibitors
- Angiotensin receptor antagonist
- Alpha-adrenoceptor antagonist
- Calcium channel blockers
- Rho kinase inhibitors
Will block stuff like NA and angiotensin II
What does contraction of vascular smooth muscle cause?
Increased vascular resistence and increase in blood pressure.
Prasozin
alpha-1-adrenoceptor antagonist
Block phenylephrine contraction
Atenolol
- beta-antagonist
- antagonist to sympathetic innervation
- prevents increases in heart rate, electrical conductivity, and contractility in the heart due to increased release of NA from the peripheral NS.
- Decrease BP
Celiprolol
it is a selective β1 receptor antagonist, but a β2 receptor partial agonist. It is also a weak α2 receptor antagonist
Labetolol
combined alpha- and beta-adrenoceptor blocking agent
Prazosin found
- Prazosin is an alpha-1 adrenergic receptor antagonist.
- Alpha-1-receptors are present on smooth muscle, as in the blood vessel walls, iris dilator muscle, and brain.
- Alpha 1 antagonists cause smooth muscle relaxation, which can, in turn, cause a decrease in blood pressure by decreasing systemic vascular resistance. This medication can also cross the blood-brain barrier
- decrease in total peripheral resistance
Atenolol found
- a beta-1 adrenergic antagonist, selectively binds to the beta-1 adrenergic receptors in vascular smooth muscle and the heart.
- block NA and ADN
- This activity results in a decrease in heart rate, blood pressure, and myocardial contractility.
Labetolol found
- alpha1-adrenergic antagonism and
- non-selective, competitive, beta-adrenergic (B1 and B2) block
- intrinsic sympathomimetic activity
- decreased peripheral vascular resistance without significantly altering heart rate or cardiac output.
*
Celiprolol found
- beta1-andrenoceptor antagonist with partial beta2 agonist activity
- reduces arteriolar resistance and improves blood flow without depressing cardiac function.
- weak α2 receptor antagonist
Block NA and ADREN
Nicorandil found
- vasodilatory drug that functions through potassium channels opener and intracellular cGMP concentrations commonly used to treat angina.
- vasodilation of arterioles and large coronary arteries
- reduces coronary vascular resistance
- stimulates guanylate cyclase to increase formation of cyclic GMP (cGMP)
- cGMP activates protein kinase G (PKG), decreases Rho-kinase activity.
- Reduced Rho-kinase activity permits an increase in myosin phosphatase activity, decreasing the Ca2+ sensitivity of the smooth muscle.[8]
nifedipine found
- inhibits the entry of Ca2+ ions by blocking these voltage-dependent L-type Ca2+ channels in vascular smooth muscle and myocardial cells.
- ↓ intracellular Ca2+ ↓ peripheral arterial vascular resistance and dilatation of coronary arteries, leading to a ↓ in systemic blood pressure and ↑ myocardial oxygen delivery.
- Nifedipine thus has hypotensive and antianginal properties.
- antagonist of the mineralocorticoid receptor,
Sodium Nitroprusside
- prodrug
- produce nitric oxide
- NO triggers intracellular cGMP-mediated activation of PKG and then inactivation of myosin light chains, resulting in relaxation of VSM
- ↓ in systemic vascular resistance (afterload), ventricular filling pressures, and systemic blood pressure with an ↑ in cardiac output.
Sildenafil found
- phosphodiesterase-5 inhibitor
- mimics (cGMP).
- accumulation of cGMP → to ↑ cGMP-dep PK activity, which phosphorylates multiple targets in SM cell.
- The result of SM cell target protein phosphorylation is a ↓ in intracellular Ca2+, ↑ efflux of K, and deactivation of myosin light chain kinase, ultimately causing SM relaxation
accu bc of inhibition
Glibenclamide
- inhibiting the ATP-sensitive potassium channels (KATP) inhibitory regulatory subunit sulfonylurea receptor 1 (SUR1) in pancreatic beta cells.
- This inhibition causes cell membrane depolarization, opening voltage-dependent Ca2+ Channels.[12]
Not a antihypertensive
Glyburide stimulates insulin secretion through the closure of ATP-sensitive potassium channels on beta cells, raising intracellular potassium and calcium ion concentrations
ODQ found
- soluble guanylyl cyclase (sGC, nitric oxide-activated enzyme) inhibitor.
*
Y-27632
ATP-competitive inhibitor of ROCK-I and ROCK-II
L-NAME
nonselective inhibitor of nitric oxide synthetases (NOS)
Acetylcholine
- decreases blood pressure by stimulating endothelium nitric oxide-dependent vasodilation in resistance arterioles
- activates guanylate cyclase, increasing cyclic GMP levels, leading to relaxation of the smooth muscle and vasodilation.
Release NO
Atropine
- blocking muscarinic receptors
- Increase heart rate
- Reduce vasodilation
