Intrinsic mechanisms of cardiovascular control that act locally, within tissues, such as paracrine chemical signals (histamine, bradykinins, prostanoids) & metabolic signals (oxygen, carbon dioxide, potassium, lactic acid) predominate over extrinsic mechanisms in control of blood flow to:
a) critical organs
b) non-critical organs
a) critical organs.
Intrinsic control via metabolic & paracrine signals over cardiovascular system predominates over extrinsic control via hormones & nervous system when blood flow to critical organs is involved.
Ie., Blood vessels to the heart, brain and working skeletal muscles will dilate or constrict depending MORE on the metabolic needs and local chemical signals than to nervous stimulation & hormones.
Conversely, blood vessels to the noncritical organs of the kidneys, splanchnic (spleen, stomach, intestines) & resting skeletal muscle will respond more to hormonal & nervous control.
Cardiac muscle is under X control, while coronary blood vessels are under Y control.
X = neurohormonal
Y = local control
Neurohormonal mechanisms control heart rate & contractility.
When these mechanisms increase HR & contractility, the metabolic rate also increases. This increased metabolic rate works through local metabolic control mechanisms to dilate critical coronary blood arterioles, which increases blood flow to the muscles of the heart.
What is the arterial baroreceptor reflex? Does it influence primarily blood flow to critical or non-critical organs?
The reflex involves presssure receptors are pressure-sensitive nerve endings in the internal carotid arteries (in the sinuses) & in the aortic arch. They respond to changes in blood pressure via stretch in the walls of the arteries by sending impulses to the CNS, which reflexively alters CO2 & vascular resistance to non-critical organs.
The lower the mean arterial pressure (MAP), the fewer the action potentials (impulses) these baroreceptors send. The higher the MAP, the more impulses.
The impulses from the aortic-arch baroreceptors travel along afferent neurons to the CNS via the vagus nerve (CN 10).
The impulses from the carotid-sinus baroreceptors travel along afferent neurons to the CNS via the glossopharyngeal nerve (CN 9).
How does the brain respond to a drop in impulses from the arterial baroreceptors?
Increase in sympathetic-nerve activity & decreases parasympthatic activity. The ONLY TWO WAYS the baroreceptors reflex can restore BP close to normal are:
1) Increase HR: SV & HR increase, so CO increases. The increase in CO restores BP toward normal.
2) Vasoconstriction: Sympathetic activity causes arterioles of NON-CRITICAL organs to CONSTRICT.
This vasoconstriction of blood vessels to non-critical organs reduces blood flow to those organs and INCREASES TPR, which helps restore arterial BP toward normal and directs blood flow to CRITICAL ORGANS.
NB: This reflex is compensatory only; it can't restore BP back to normal on its own, only improve situation. However, it is very rapid & plays the main role in making short-term, minute-by-minute adjustments to BP eg. in standing, posture, etc.
Which is the major mechanism responsible for setting the long-term level of arterial blood pressure?
a) arterial baroreceptor reflex
b) atrial volume receptor reflex
c) autonomic nervous system
d) none of the above
d) None of the above.
Both the arterial baroreceptor reflex and the atrial volume receptor set in motion the renin-angiotensin-aldosterone system, while the atrial volume receptor induces the release of anti-diuretic hormone (ADH) from the posterior pituitary (it is secreted by the neurons of the hypothalamus). These are only short-term fixes.
The ensuing vasoconstriction of arterioles in non-critical organs and the retention of sodium and water in the DCT & collecting ducts conserves blood volume in the event of falling BP.
These help bring BP back toward normal, but what is required over the longer term are:
1) thirst reflex, to drink more water
2) restoration of lost plasma proteins and blood cells - can several days of synthesis of proteins in liver and weeks of erythropoesis in bone marrow
What are the neurotransmitters released by sympathetic neurons and parasympathetic neurons in the cardiovascular system?
Aside from being released as a neurotransmitter by sympathetic neurons, where else is norepinephrine made? How is it released and transmitted in the cardiovascular system?
Norepinephrine and epinephrine are made in the adrenal medulla. They are stimulated by sympathetic nerve impulses to be released into the blood, where they travel through the circulation lightly bound to plasma proteins. They bind to cell-surface receptors (GPCR) called adrenergic receptors.
What are the two main subtypes types of adrenergic receptors?
alpha & ß
How are the alpha & beta adrenergic receptors further subdivided?
What type of receptors does Acetylcholine activate?
What are the two major subtypes of these Ach receptors?
Subtypes: Muscarinic & Nicotinic
What subtype of cholinergic receptors mediate most of acetylcholine's effects in the cardiovascular system?
Muscarinic, aka M receptors.
There are five subtypes of muscarinic cholinergic receptors. What types have the greatest cardiovascular importance?
M2 & M3
In the cardiovascular system, it's less important to make a distinction between alpha-1 & alpha-2. Where are they located? How are they innervated, and what is their general effect when bound to their ligand?
Both alpha adrenergic receptors are found on the cell membranes of smooth-muscle cells of arterioles in ALL ORGANS (critical & non-critical).
They are also found on smooth-muscle cells of abdominal veins.
These receptors are innervated by post-ganglionic SYMPATHETIC NEURONS & thus when they bind to the sympathetic-system neurotransmitter norepinephrine or circulating norepinephrine & epinephrine, VASOCONSTRICTION of arterioles or veins occurs.
Vasoconstriction of arterioles increases TPR & reduces blood flow to organs, enabling diversion to others.
Venoconstriction of veins decreases peripheral venous blood flow but displaces it toward central circulation (heart & lungs), increasing ventricular pre-load & SV.
Which receptor is responsible for conveying sympathetic control of the heart? Specifically, CARDIAC MUSCLE?
ß-1 adrenergic receptors
These are found on cell membrane of every cardiac muscle.
What activates ß-1 adrenergic receptors, and what are the main effects when they bind to their main ligand?
ß-1 adrenergic receptors are activated by norepinephrine as neurotransmitter released by sympathetic neurons or circulating norepinephrine & epinephrine from the adrenal medulla.
Activation of ß-1 receptors result in increase of pacemaker rate and conduction velocity of action potentials, as well as decrease in refractory period, so you get a faster heart rate.
Contractility also increases with more calcium ions released into the muscle cells, so stroke volume increases.
Ie., increased SV & HR = increased CO
Where are ß-2 adrenergic receptors, and what are the main effects when bound to their ligands?
Why are the effects so different from those caused by binding of ß-1 adrenergic receptors?
ß-2 adrenergic receptors are located on ARTERIOLES of the coronary circulation (blood to the heart muscles) and skeletal muscles.
Unlike ß-1 adrenergic receptors, ß-2 only bind to norepinephrine & epinephrine in the circulation from the adrenal medulla, as they are NOT innervated by sympathetic neurons.
These hormones are released by the adrenal medulla during fight, flight or trauma, and so they DILATE coronary blood vessels and arterioles supplying skeletal muscle. Thus blood flow to heart & muscles increases as needed to respond to fight or flight.
In emergency situations, ß-2 adrenergic receptors can over-ride the the vasoconstriction caused by alpha-1 & alpha-2 receptors in the arterioles of the coronary circulation and skeletal muscle.
M2 cholinergic receptors are found mostly in which type of cardiac muscle cells?
a) Sino-atrial node
b) Atrioventricular node
a, b & c - SA & AV node cells & atrial cells
These are heavily innervated by parasympathetic neurons, which release Ach as their natural neurotransmitter. There are not many parasympathetic neurons innervating the muscle cells of the ventricles.
What are the main effects of Ach binding to M2 cells heart?
Basically the opposite of norepinephrine binding to ß-1 receptors.
Little direct effect on contractility since there are not very many parasympathetic neurons in the ventricles.
Indirectly, Ach released from the few parasympathetic neurons in the ventricles end up binding to M2 receptors on SYMPATHETIC nerve terminals instead, inhibiting release of norepinephrine from the sympathetic neurons. This indirectly weakens sympathetic activity on ventricular muscle cells.
What are the differences between M2 & M3 cholinergic receptors?
M2 cholinergic receptors are basically the parasympathetic nervous system's answer to the sympathetic nervous system's ß-1 receptors in cardiac muscle. Binding of Ach by M2 receptors leads to reduced HR, reduced SV & CO, mainly through actions in the atria, and indirectly in the ventricles.
M3 receptors are basically the parasympathetic nervous system's answer to alpha-1 & alpha-2 adrenergic receptors that cause vasoconstriction in arterioles everywhere. Binding of Ach by M3 receptors leads to VASODILATION in arterioles of the coronary arteries, genitals, skeletal muscle & most other organs.
These receptors actually constrict vascular smooth-muscle cells, but this effect is OVER-RIDDEN by the activated receptors' ability to induce vascular endothelial cells to secrete vasodilatory nitric oxide (NO).
Unlike M2 receptors, whose actions are brought on by Ach exclusively, Ach-activated M3 receptors bring on their vasodilatory effects through NO, and the stimulation of more NO release by vascular endothelial cells.
NB: In external genitalia, parasympathetic neurons release BOTH Ach & NO as neurotransmitters.
In some non-primates, sympathetic neurons in skeletal muscle release Ach instead of norepinephrine as their main neurotransmitter. These are called sympathetic cholinergic neurons & when bound by Ach, they cause anticipitory vasodilation of arterioles in skeletal muscle ahead of exercise or fight/flight response.