Lecture 18 Flashcards
Sympathetic activity in CVD?
Can record SNS activity directly. Can record muscle SNS activity (tends to show the same trends with renal and CV). Skin SNA is about controlling the blood flow for thermo control (controlled by different regions of the brain).
Where is the autonomic activity coming from for the heart?
The heart is innervated by the parasympathetic system (vagus nerve). The heart also receives sympathetic activity.
What neurotransmitters are involved?
Somatic - there is just one simple neurotransmitter and that is ACh.
Autonomic - there is SNS and PNS.
PNS - both transmitters are ACh.
SNS - for SM, CM and gland the preganglionic fibres release ACh and the psotganglionic fibres release Norepinephrine. For the adrenal gland the preganglionic fibres relate ACH and the postganglionic fibres release epinephrine.
Describe the receptors for ACh?
- Nicotinic receptors - respond to nicotine. Find on skeletal muscle (N1/Nm) and autonomic ganglia (N2/Nn). Curare will block this receptor - often used to paralyse people.
- Muscarinic receptors - respond to muscarine. Find on PNS target tissue. Atropine will block this receptor - use in CVS to increase HR.
What are the clinical uses of drugs that target nicotinic receptors?
- Ganglion blockers - drugs that act as antagonists at Nn. Previously used to treat hypertension but they’re not well tolerated. Could use this in a hypotensive crisis in a hospital situation (only used in a crisis situation).
- Neuromuscular blockers - drugs that are competitive antagonists at the Nm receptors that cause neuromuscular blockade e.g. tubocurarine used as muscle relaxants in surgery.
Describe atropine (muscarinic antagonists)?
It is a muscarinic antagonists. Blocking the effect of slowing the HR, before increasing the HR. It increases the firing in the SA node as well s the AV node. It also:
1. dilates pupils.
2. inhibits salivary, sweat and mucus gland secretions.
3. treatment for poisoning by organophosphate insecticides and nerve gases.
Used in a crisis situation. Derived from deadly nightshade (poisonous flower). It blocks the effects of the PNS (dry mouth - as blocking the effect of the digestive system).
Describe adrenergic receptors?
Alpha and beta-adrenoreceptors. The noradrenaline diffuses into the synaptic cleft to bind onto the postsynaptic cell.
- Alpha - noradrenaline - adrenaline - isoproteronol. Found mainly in vascular smooth muscle.
- Beta - isoproteronol - adrenaline - noradrenaline. Found mainly in the heart.
Describe adrenoceptor agonists?
alpha-1-agonists - phenylephrine, oxymetazoline.
alpha-2-agonists - clonidine - cause fall in bp partly due to decreased NA release, major central actions (make people sluggish).
beta-1-agonists - dobutamine - increased cardiac contractility, but cause dysrhythmias.
beta-2-agonists - salbutamol - bronchial dilator - asthma.
How does the autonomic nervous system control HR?
The pace is set by the SA node (intrinsic to the heart itself). The SA node is innervated by both the vagus nerve and sympathetic nerves. Increase vagal activity - decrease HR very quickly. Increase SNS activity will lead to an increase in HR (however it takes longer for you to see the full effect).
What happens when we stimulate the vagal nerve?
We increase the outward potassium current (this makes the cell more hyper polarised - more negative as more potassium is going out), we also decrease the funny current so the speed at which sodium is coming into the cell has slowed down. Slower to reach the threshold for the AP to occur. Thus HR slows down.
What happens when we stimulate sympathetic nerves?
Increase the rate of the funny current, more sodium moving in quicker (reach threshold quicker). The heart rate increases, and there is an increase in the calcium transient current.
Describe neural control of stroke volume?
The more you fill the heart - the stronger the contraction. At any given strength, the higher the norepinephrine content that stronger the stretch - thus the stronger the force. NE binds with beta receptor, cAMP (secondary messenger) will increase the calcium coming in, this will increase release of calcium by SR (due to greater SR uptake). cAMP also increases SR release of calcium by an (increase in phospholamban (more calcium ready to come out at next contraction). There is also a HR effect, so less time to get rid of the calcium (increase in HR = stronger contraction).
Describe beta-blockers?
Used in heart failure (chronic) - reduces the work the heart has to do; so reducing the oxygen needs of the cardiac muscle. Examples: atenolol; labetalol, metoprolol succinate; metoprolol tartrate; nadolol etc. The most effective treatment in preventing death in heart failure, as they reduce workload and prevent arrhythmias.
Describe the effect of sympathetic activity on TPR?
We up regulate and downregualte tone in smooth muscle. Increase SNA we can increase vasoconstriction. The higher the sympathetic tone the higher the blood pressure.
Describe the process of vasoconstriction?
NE acts on alpha1 receptors on your smooth muscle, this will cause an increase in IP3, which will cause an increase in calcium release, this will cause contraction.
