pharmacology of blood vessels

where do arteries carry blood

carry blood away from the heart, towards organs and tissues

arterial blood is normally oxygenated but there is one exemption. what is the artery that carries deoxygenated blood

pulmonary arteries - deoxygenated blood from heart to lungs

how do arteries branch in capillaries

elastic arteries → muscular arteries → arterioles → capillaries

role of capillary

vessels which bridge the arterial and venous systems

what type of muscle do walls of arteries, arterioles, venules and veins contain

smooth muscles

how is the contractions of blood vessels controlled

by mediators released:

• locally from sympathetic nerve terminals

• circulating hormones

• endothelial cells

true or false: parasympathetic nerves are important in controlling vascular smooth muscle tone

false - parasympathetic not important

blood vessels have 3 layers, name each layer

• tunica intima

• tunica media

• tunica adventitia

describe the tunica intima

• inner lining of endothelial cells

• thin layer of fine connective tissue dominated by elastic fibres

describe the tunica media

• large elastic arteries

• smaller vascular arteries

middle layer

• large elastic arteries

  • e.g. aorta

  • high proportion of elastic tissue

• smaller vascular arteries

  • large amount of smooth muscle

where do veins carry blood

carry deoxygenated blood from tissues to heart and lungs

veins normally carry deoxygenated blood, what vein is the exception

pulmonary vein carries oxygenated blood from lungs to heart

veins have the same 3 layers as arteries (tunicae) but how does it differ

veins transport blood at a lower pressure - not as strong

difference between the venous walls and arterial walls

venous walls are:

• thinner

• contain less elastic, collagenous and smooth muscle tissue

• easily distensible and compressible

why does the blood in veins give the vessels a blue colour

because it lacks oxygen and walls of veins are thin

what valves keep venous blood moving in the right direction

• semilunar valves keep blood flowing towards heart

what assists venous blood flow

• pumping action of skeletal muscle contraction

• thoracoabdominal pump

what happens to pressure in thoraic activity during inspiration and what effect does this have on blood

• pressure decreases → pulls blood into inferior vena cava

true or false: on exhalation, blood is forced into right atrium

true

why does the venous system act as a blood reservoir

total blood volume is unevenly distributed between arteries, veins and capillaries

arterioles determine peripheral resistance (PR), why is control of PR important in treatment of hypertension and angina

because PR determines arterial pressure and regulates blood flow through individual organs

cardiac output also affects blood pressure. what does cardiac output depend on

stroke volume and heart rate

• sv x hr = co

overall, what is the equation to determine bp

bp = co x pr

blood pressure = cardiac output x peripheral resistance

what does stroke volume depend on 

plasma volume and venous return

how does these factors affect heart rate

• sympathetic

• parasympathetic

• sympathetic: increases heart rate

• parasympathetic: decreases heart rate

what is vascular tone

he degree of contraction in the smooth muscles of blood vessel walls, which determines the vessel's diameter and affects blood pressure

vascular tone is regulated by many different systems. how do sympathetic nervous affect vascular tone

sympathetic nerves secrete noradrenaline which leads to vasoconstriction

vascular tone is regulated by many different systems. how do vascular endothelium affect vascular tone

• secrete nitrous oxide (NO) which causes vasodilation

• secretes endothelin mediator which controls vasoconstriction

what causes vasoconstriction of blood vessels

• sympathetic nerves secrete noradrenaline

• endothelium secretes endothelin mediator

what causes vasodilation of blood vessels

• endothelium secretes NO mediator

vascular tone is regulated by many different systems. how do circulating hormones affect vascular tone

• adrenal medulla secretes adrenaline (causes vasodilation or vasoconstriction depending on receptor type)

  • beta-2 receptors = vasodilation

  • alpha 1 receptors = vasoconstriction

• renin-angiotensin aldosterone system (RAAS) secrete aldosterone

  • indirectly causes vasoconstriction by increasing sodium and water retention which raises bp

name the 3 systems that regulate vascular tone

• sympathetic nerves

• vascular endothelium

• circulating hormones

what ion triggers vascular smooth muscle contraction

Ca2+

does vasoconstriction or vasodilation occur if:

• [Ca2+] rises

• [Ca2+] decreases

• [Ca2+] rises: vasoconstriction

• [Ca2+] decreases: vasodilation

entry and exit of Ca2+ ions across plasma membrane occurs through which channels and when are they opened

• occurs through voltage gated Ca2+ channels

  • open when cell is depolarised

  • influenced by GPCRs

• receptor-operated channels

how is Ca2+ ion exit controlled 

mediated by Na+/Ca2+ ATPase and Na+/Ca2+ exchange

what is the main storage site of Ca2+ in vascular smooth muscle

sarcoplasmic reticulum

many vasoconstrictors activate which compound

membrane-bound phospholipase C

how do vasoconstrictors activate phospholipase C

through GPCRs

what does activation of phospholipase C leads to

increased levels of IP3 which leads to receptor mediated release from sacroplasmic reticulum into cytoplasm

how is the released Ca2+ recaptured to the sarcoplasmic reticulum

by ATP-driven active transport system which is controlled by cAMP and cGMP

how do vasoconstrictors cause vascular smooth muscle contraction

1) IP3-mediated intracellular Ca2+ release from sarcoplasmic reticulum

2) membrane depolarisation (Ca2+ influx)

3) receptor-operated Ca2+ entry

why are endothelin concentrations higher in heart failure and hypertension

because endothelin is made in response to vasoactive mediators released following trauma, platelets, endotoxin and thrombinwhat

what inhibits endothelin synthesis

NO, natriuretic peptides (e.g. ABP, PGE2, PGI2

how do smooth muscle differ from striated and cardiac muscles

smooth muscles do not contain troponin

how does Ca2+ cause smooth muscle contraction

• Ca2+ binds to calmodulin 

• activates myosin light chain kinase (MLCK)

• this phosphorylates myosin light chains

• enables myosin and actin to interact

• causes contraction

what causes relaxation of vascular smooth muscles

decreased [Ca2+] → myosin phosphatase enzyme dephosphorylates myosin

• [decreased/increased] myosin phosphatase activity or [decreased/increased] MLCK activity results in Ca2+ desensitisation

• [decreased/increased] myosin phosphatase activity or [decreased/increased] MLCK activity results in Ca2+ sensitisation

• [decreased/increased] myosin phosphatase activity or [decreased/increased] MLCK activity results in Ca2+ desensitisation

• [decreased/increased] myosin phosphatase activity or [decreased/increased] MLCK activity results in Ca2+ sensitisation

how do vasodilators cause vascular smooth muscle relaxation

1) Inhibit Ca2+ entry though voltage gated Ca2+ channels by calcium channel blockers

2) increase intracellular cAMP or cGMP concentration

3) indirectly hyperpolarising membrane (K+ channel activators)

what enhances Ca2+ efflux

cAMP causes inactivation of MLCK which enhances Ca2+ efflux

what does cGMP do

opposes agonist-induced increases in [Ca2+]

how do vasodilators reduce cardiac workload

decreasing pre-load (reducing filling pressure) and after-load (reduced vascular resistance)

how do vasodilators decrease pre-load and after load

• reducing central venous pressure

• reducing arterial pressure

• increasing local tissue blood flow

which conditions are vasodilators clinically important for

• hypertension

• angina pectoris

• cardiac failure