CVS: Vascular Tone and Smooth Muscle Flashcards
What is vascular tone?
Vascular tone is the degree of constriction of a blood vessel relative to max dilation. Controlled by vsm.
This means that blood vessels have a resting tone, where they can dilate or constrict further
Regulation of vascular tone (controlling blood vessel radius) is central for controlling bp and blood flow (Darcy and Pioseuille’s law)
Which blood vessels have vascular tone?
Vascular tone present in arteries, arterioles, veins. Capillaries do not contain vsm so not have vascular tone.
Vascular tone in arterioles is important in controlling TPR and therefore blood flow to end organs (blood flow directly proportional to r^4)
Regulating vascular tone is a important target in treating cardiovascular disease
Why do you need extrinsic and intrinsic control of vascular tone?
Intrinsic controls like the role of endothelium, immune cells, platelets, stretch all regulate local blood flow to tissues. This (regional hyperaemia)= important
Extrinsic controls regulate TPR to control bp. BP is the drive for blood flow. Brain alters blood flow to organs according to need e.g. During exercise, hypovolemia etc. This is v important
What are extrinsic controls of vascular tone?
Nerves: Vasoconstrictors, e.g. noradrenaline. Vasodilators, e.g. Ach, NO
Hormones: Vasoconstrictors – e.g. adrenaline, angiotensin
Describe how neurotransmission at the pre and post synaptic membrane can cause vasoconstriction and vasodilation
Pre-synaptic membrane:
AngII acts on AngI to increase NA release (increase RAAS symp activity).
α2 at the PREsynaptic terminal reduces NA release
Local K+/adenosine levels etc reduce release of NA – important vasodilatation pathway
Post-synaptic membrane: NA and ATP released across the synaptic cleft and binds to these receptors in blood vessels:
α1, α2 (contraction). β2 (relaxation if present in some blood vessels)
What are important points to remember about the sympathetic vasoconstrictor nerves?
Controlled by brainstem: RVLM (vasomotor centre), controlled by CVLM, hypothalamus. Controls BF and BP
Innervates most arterioles & veins: NA activates a1-adrenoceptors on vsmcs to cause vasoconstriction
Symp activity is TONIC (fires ~1 action potential / s) to release a bit of NA. Tonic symp activity sets vascular tone. So, a FALL in ongoing symp activity= dilatation
What are the roles of symp vasoconstrictor nerves?
Contract arterioles to produce vascular tone. This maintains arterial BP and blood flow to brain/myocardium
Symp pathways innervate diff tissues- can vasoconstrict some vessels and vasodilate others e.g. During hypovolemia, increase sym stimulation to GI (less blood flow). Reduce sym nerve stimulation to brain/heart (more protective BF)
Produce pre-capillary vasoconstriction. This reduces capillary pa relative to oncotic pa which increases interstitial fluid reabsorption. Maintains blood volume
Produces venoconstriction to increase venous return. Increases stroke volume via Starling’s law
Describe the 3 main vasoconstrictor hormones
Adrenaline (Adr): Released due to symp stimulation from adrenal glands. Acts on a1-adenoceptors on vsm
AngII: V potent vasoconstrictor. Acts on AT1 receptors on vsm. Ang II also increases BV/CO, increasing TPR and so BP
Vasopressin: Released from posterior pituitary. Acts on V1-receptors on vsm. Also acts on V2 receptors in the kidneys to increase H20 reabsorption and thus blood vol.
What are other important vasoconstrictor hormones?
Endothelin-1 (ET1): Released from endothelium. Acts on ETA receptors on vsm.
Thromboxane (TXA2): Released from aggregating platelets. Acts on TP receptors on vsm. Important vasoconstrictor alongside clotting process
How exactly do the vasoconstrictors increase vascular tone?
Vasoconstrictor receptors= a1, AT1, V1, ETa, TP all stimulate Gq pathway to increase vascular tone:
Gq activates PLC which causes a breakdown of PIP to into IP3 and DAG. These messengers act on ion channels to produce depolarisation, activating vgcc to bring Ca2+ into the cell. Rise in Ca-M drives the MLCK reaction, more actin-myosin interactions and therefore contraction
What is atrial natriuretic peptide?
Increased filling pressures (from increased blood vol) causes specialised atria myocytes to secrete ANP. This stimulates stretch receptors which acts at NP receptors on vsm (Activate cGMP pathway like NO)
How does ANP decrease blood pressure?
Reduces BP by:
Systemic vasodilation – opposes action of NA, Adr, Ang II, ADH, ET-1, TXA2
Dilation of renal afferent arteriole – increases GFR, Na+ and H2O excretion, reduces blood volume
Decreases release and actions of aldosterone, renin, ADH
When and why do Adrenaline and Noradrenaline have different responses on arterioles?
Adrenaline has higher affinity for b adrenoceptors. NA has higher affinity for a adrenoceptors
a1 adrenoceptors produce contraction, b2 receptors produce relaxation
Skeletal muscle and coronary arteries have more b2 than a1 adrenoceptors
So giving adrenaline mainly acts at b2 to dilate vessels. Giving NA mainly acts at a1 receptors to constrict vessels in skeletal muscle and coronary arteries
What are important pharmacological vasoconstrictors agents? In which context would you use each drug?
NA is given to act at a1-adrenoceptors on VSMCs to increase TPR and BP. It has no significant actions on heart (b1) so doesn’t make the heart work hard to increase BP, blood flow. More cardiac protective, important in sepsis, severe heart failure
Adrenaline is given in high concs to act on both b1 on the heart and a1 on VSMCs to raise BP (also b2 in lungs for bronchodilation) e.g. epipen for anaphylaxis
Vasopressin (ADH): Can also be given in sepsis
