neurohormonal control of BP Flashcards
PO 147 (add)
What factors determine blood pressure?
overview
Cardiac Output (HR x SV) and vascular resistance
HR - metabolic and hormonal see rest of cards
SV - ESV and EDV, determined by preload, contractility and afterload, see cards on cardiac function
SVR - Vascular diameter changes by activation of vascular smooth muscle by:
• autonomic nerves
• metabolic and biochemical signals
• release of vasoactive substances by vascular endothelium (lines the blood vessels)
Vascular endothelium releases:
• vasoactive substances as above
• nitric oxide (NO) - relax
• endothelin-1 (ET-1) - contract
• prostacyclin (PGI2) - relax
These modulate:
• cardiac and vascular function
• hemostasis (blood clotting)
• inflammatory response
PO 1.48 (add)
Discuss the cardiovascular responses to exercise
Increased blood flow to skeletal muscle by arterial dilation
Arterial pressure be maintained by increase CO and vessel constriction of other organs
PO 1.47
factors that regulate and control BP
MAP (-CVP) = CO x SVR
Summary of neurohormonal influences
Neurohumoral mechanisms act through changes in vascular function (SVR, venous compliance), blood volume and cardiac function to regulate BP so body can adjust to changes in body posture, physical activity or environmental conditions.
- fast include autonimc nerves and catecholamines
- slow (hours to days) include ones that change blood volume
Sensors include:
- baroreceptors
- volume receptors
- chemoreceptors
- osmoreceptors
PO 1.47
What factors determine systemic blood pressure regulation and control?
CNS control
Controlled by CNS
o medulla oblongata in brainstem
- cell bodies for parasympathetic and sympathetic afferents
o hypothalamus
- has thermoreceptors and modulates medulla neuronal activity to modulate sympathetic outflow to cutaneous circulation
- flight or fight response in exercise – input to medulla for sympathetic mediated tachy, ionotropy, catecholamine relseae and systemic vasoconstriction
o cortical regions
- connects with hypothalamus and medulla to alter function in emotion (fear, anxiety)
- fear – vagal activation and withdrawal of sympathetic - vasovagal syncope
- fear anxiety – sympathetic activation, if prolonged can get hypertension, hypertrophy and arrhytmias
- CNS receives afferent input from peripheral and central sensors
- Baroreceptors (peripheral)
- Afferent via NTS to medulla
- Chemoreceptors (peripheral)
- Afferent via NTS to medulla
- NTS
- Inhibitory interneurons project to cell bodies of sympathetic
- Excitatory interneurons project to cell bodies of parasympathetic nerves
PO 1.47
factors that regulate and control BP
baroreceptors - high pressure
- stretch receptors in blood vessels and heart, control BP via closed loop negative feedback system. MAP = CO x SVR and blood volume
- located in carotid sinus and aortic arch
- beat to beat control, rapid, by altering CO and SVR
- afferents
- carotid sinus via sinus to glossopharyngeal (IX) to NTS of medulla
- aortic arch joins with vagus (X) to NTS of medulla
• integration
- NTS stimulates GABA inhibitory neurons to decrease sympathetic tone
- NTS excitatory to nucleus ambigus increasing sympathetic tone
• Efferents
- Sympathetic projects pre ganglionic neurons into grey column of spinal cord, synapse with post ganglionic neurons in paravertebral sympathetic chain (stellate and cervical to heart, thoracic to heart and vessels) and prevertebral ganglia to vessels – cause increased HR, contractility→increased SV and CO→increased MAP. Vaso and veno constriction (or vasodilation to certain tissues), increased SVR →increased MAP
- Parasympathetic via vagus to heart to decreased rate, contractility → decreased SV and CO →decrease MAP. Vasodilate →decreased SVR → decrease MAP
- At normal BP tonically active, inhibit sympathetic output and stimulate vagal
- Increased BP (MAP or pulse pressure, image 59) or carotid sinus massage increases firing, stretches receptors, further inhibition of sympathetic and activation of vagal
- Set point 95mmHg is set point, point of max sensitivity, small deviation from here causes large change in rate of firing
- o >150mmHg, no further increase
- o <30mmH, no further decrease
- this point can re set to the right in hypertension in 1-2 days, aterioscleoris causes less stretch so decreased sensitivity
- aortic arch has higher threshold, less sensitive, secondary baroreceptor
• can test baroreceptor function with valsalver manourver, should make R-R ratio >1.5
PO 1.47
factors that regulate and control BP
baroreceptors - low pressure
- stretch receptors in blood vessels and heart, control BP via closed loop negative feedback system. MAP = CO x SVR and blood volume
- located in atria, ventricles and pulmonary vessels
- more involved in altering blood volume over hours to days by detecting increased or decreased volume
- afferents
- type A, fire in atrial systole (A wave)
- type B, fire in atrial villing (V wave)
- increased filling in low HR increases firing, afferent via vagus to medulla
- integration as above
- efferent
- sympathetic to SA node to increase HR
- decrease ADH release from posterior pituitary so diuresis
- decreases sympathetic to kidney, to decrease ANII and aldosterone release
• can re-inforce or oppose high pressure baroreceptors activity
- in heart failure increased firing of these opposes decreased firing of arterial baroreceptors because arterial pressure is low
- in haemorrhage decreased firing reinforces decreased firing of arterial baroreceptors
PO 1.47 factors that regulate and control BP
Sympathetic nervous system
- Autonomic nervous system regulates involuntary body function (heart, intestines).
- Made of sympathetic and parasympathetic.
- Both supply heart and have opposing actions.
- Parasympathetic predominates at rest
- Increased activity of one decreases activity of the other
o Peripheral receptors via NTS
o Origin
- Interconnected neurons in rostral ventrolateral medulla, cardiostimulatory centre/pressor centre/vasoconstrictor centre
o Preganglionic fibres
- from medulla down intermediolateral grey columns of spinal cord and exit at T1 – L2, glutamate is the excitatory transmitter
o Ganglia
- paravertebral ganglia (cervical, stellate and thoracolumbar sympathetic chains) on either side of spinal cord with Ach via a nicotinic receptor
- OR prevertebral ganglia in abdomen (celiac, superior and inferior mesenteric)
o Post ganglionic
- efferents to adventitia of arteries, veins, and cardiac plexus - SA (right – affect HR ) and AV nodes, conduction system, myocytes (left – contractility) and coronary vasculature
o Effect
- NE synapses on myocyte post junctional B1 >B2 adrenoceptors
- Stimulates GS protein, enhances adenyl cyclase to increase cAMP, activates protein kinase A to increase open L type Ca++ and increase intracellular Ca++ and SR release of Ca++
- Increased trop C affinity for Ca++, increase reuptake into SR
- Increased trop I and phospholamban ? (doesn’t phospholamban inhibit SERCA so less contraction)
o End result
Heart
- Increases chronotropy
- Dromotropy
- inotropy
- Pre junctional B2 facilitate NE
- Prejunctional A2 inhibit NE
Vessels
- Constrict and increased SVR and VP, decrease venous capacitance so increased venous pressure by NE to postjunctional a1 (more than postjunctional a2)
- Vasodilation when NE and adren bind to B2 (if not opposed by alpha vasocontrction as usually is)
- Vasoconstrcion and decreased perfusion to most organs except heart and brain – get vasodilation after initial vasoconstriction due to metabolic factors so increase perfusion
o Duration – slow but long lasting
- As action via 2nd messenger
- Offset as NA reuptaken into nerve terminal or carried away in blood stream
o RANDOM: Neurotransmitter release form varicosities – enlargements along the nerve fibre
PO 1.47 factors that regulate and control BP
Parasympathetic nervous system
- Autonomic nervous system regulates involuntary body function (heart, intestines.
- Made of sympathetic and parasympathetic.
- Both supply heart and have opposing actions.
- Parasympathetic predominates at rest
- Increased activity of one decreases activity of the other
o Afferent from periph baroreceptors, excitatory from NTS
o Efferents from hypothalamus also modulate
o Origin
- Cell bodies in medulla are called dorsal vagal nucleus or nucleus ambiguous – cardioinhibitory centre
o Preganglionic
- Efferents exit the medulla through foramen magnum as CN 10 and go to heart close to common carotid through mediastinum as L and R vagus nerve
o Ganglia
- Synapse near the target tissue on epicardium via nicotinic receptors using Ach and form small ganglia
o Postganglionic
- short fibres sprout to go to SA (right) and aVN (left), conduction pathway, myocytes (atria more than ventricles) and coronary vasculature
o Effect
- Release acetylcholine, binds to M2
- M2 stimulates Gi proteins, decreased adenyl cyclase, decrease cAMP levels
- Enhances K+ efflux hyperpolarizes cell membrane
o End result
Heart
- Neg chronotropy - heart rate via SA node inhibition
- Neg dromotropy - conduction velocity through AV node
- Minor Neg ionotropy – contractility via effect on ventricular myocytes
Vessels
- Direct vasodilation (genetialia) through release of AcH to M2 on vascular endothelium causing formation of NO
- Indirect vasodilation (gastrointestinal) by stimulating non vascular tissue to produce vasodilators like bradykinin
- Regulate blood flow to specific organ rather than regulate SVR and arterial BP
o Duration – rapid but short lived
- Ach activates K channel via Gs protein, no secondary messenger
- Anticholinesterase in SA and aV nodes means quick breakdown of Ach
- Parasympathetic suppression of norad release
PO 1.47 factors that regulate and control BP
chemoreceptors
o peripheral on arteries
- in carotid bodies near bifurcation exterinal and internal carotid arteries
- afferent joins sinus then glossopharyngeal nerve to synapse in medulla
- increased firing to decreased pO2 (<80mmHg), increase pCO2 (>40mmHg) and acidosis (ph<7.4), hypotension from decrased perfusion
- also in aortic bodies, afferent to medulla travel with vagus
o central in medulla
- increase firing with hypercapnia and acidosis but not directly to hypoxia
- CO2 from blood into CSF forms hydrogen ion by the bicarbonate buffer, this ion stimulates the receptor rather than CO2
o Increased resp activity and stimulates sympathetic activity to heart and systemic vasculature to increase BP. Sympathetic does not increase HR tho, it is the resp stimulation activating stretch receptors that causes the tachycardia
PO 1.47 factors that regulate and control BP
Other reflexes
o Cushing reflex – increased ICP, brain ischemia stimulates medullary center, get sympathetic mediated pressor response and baroreceptor mediated bradycardia
o Cerebral ischemia – if MAP <60mmHg, sympathetic constriction of systemic circulation and MAP can rise to 200mmHg
o Pain
- AMI causes sympathetic activation, high BP, tachy and diaphoresis, BP mite still drop if ischeamia decreases cardiac output
- Trauma or visceral distension causes hypotension enhanced by parasympathetic
- Cold pressore response – sympathic activation and high BP if put hand in water
o Bezold jarisch reflex from dye in coronary arteries in angiogram or inferoposterior LV ischeamia – vagus brady and hypo
o Pulmonary stretch receptors in airways and resp muscles inhibit medullary sympathetic centre – drop BP, reflexive increase in HR with normal respiration
o Muscle and joint stretch receptors – activation of sympathetic with movement
o Diving reflex – underwater, thermoreceptors on face via facial nerve to brainstem, vagal slows HR and sympathetic peripheral vasoconstriction to reduce O2 consumption but preserves coronary and cerebral blood flow. Enhanced by breath holding
o Thermoreceptors in skin and hypothalamus – if decreased temp get cutaneous vasoconstriction
PO 1.47 factors that regulate and control BP
humoral control
can directly influence cardiac and vascular function or indirectly influence blood volume
circulating catecholamines
Other hormones can also have direct or indirect effects
o thyroxine
o estrogen
o insulin
o growth hormone
o Release from adrenal medulla
- (80% epinephrine, 20% norepinerphine)
- when preganglionic sympathetic nerves activate this tissue in stress – exercise, heart failure, blood loss, stress, excitement, pain
- pheochromocytoma – adrenal tumor, increased catecholamine release, tachycardia, arrhythmia, hypertension
o From sympathetic nerves innervating blood vessels
- Mostly noradrenaline
- Most of it taken but up by nerves but some diffuses into blood, this amount increases lots when high levels of sympathetic nerve activation
o Adrenaline image 62
- Binds B1, B2, > A1, A2
- At low concentrations binds B preferentially
- So get chronotropy, inotropy and dromotropy (B1) and vasodilation of skeletal muscle (B2). MAP unchanged, pulse pressure increased (increased SV)
- • At high concentrations bind B and A
- • So get cardiac stimulation (B1) and vasoconstriction (A). MAP increases
o Noradrenaline image 63
- Binds B1, A1 > B2, A2
- Increases pulse pressure (increased SV) and MAP (vasoconstriction)
- Initial increase in HR (B1)then decrease cos high MAP increases baroreceptor firing so vagal decrease HR
o Other actions
- Stimulate renin release
- Increased angiotensin II and aldosterone
- Cardiac and vascular smooth muscle hypertrophy and remodeling
PO 1.47 factors that regulate and control BP
humoral control
can directly influence cardiac and vascular function or indirectly influence blood volume
renin-angiotensin-aldosterone system
o renin and angiotensin formed in many tissues, most important is kidney – juxtaglomerular cells release renin
o renin release stimulated by
- B1 sympathetic stim of kidney
- Renal artery hypotension
- Decreased Na delivery to distal tubules (from redueced GFR from reduced renal perfusion)
o juxtaglomerular apparatus
- juxtraglomerular cells near macula densa and afferent and efferent arteriols of glomeruli
- macula densa of distal tubule sense NaCl
o renin makes angiotensinogen (from the liver) into Angiotensin I
o angiotensin converting enzyme (ACE) from vascular endothelium (espec lung) converts AN1 to AN II
o AN II acts on its receptors AT1
- Constricts resistance vessels by binding to AT1 receptors, increased SVR and BP
- Facilitates noradrenaline release from nerve endings and inhbitits noradrenaline re-uptake by nerve endings – enhaces sympathetic adrenergic affects
- Makes adrenal cortex release aldosterone, which increases Na and fluid retention and blood volume (excrete K)
- Vasopressin released from post pituitary, increased blood volume
- Stimulates thirst center, increased blood volume
- Stimulates cardiac and vascular hypertrophy
o AN II basally excreted, increased in exercise, standing, dehydration, loss of blood volume
o Diseases and drugs
- Secondary hypertension from renal artery stenosis
- Primary hyperaldosteronisum from adrenal tumor causes hypertension (depresses renin and AN II cos of high BP)
- Heart failure – low renal perfusion so increased ANII and symp activation, hypertension
- ACE inhibitor, stops formation ANII, less sympathetic activation
- AT1 receptor blocker, less sympathetic activation, reverse cardiac and vascular remodeling from chronic hypertension and heart failure
PO 1.47 factors that regulate and control BP
humoral control
can directly influence cardiac and vascular function or indirectly influence blood volume
Atrial natriuretic peptide
o synthesized, stored and released by atrial myocytes, 28 amino acid peptide
o released
- atrial distension
- ANII stimulation
- Endothelin stimulation
- Sympathetic stimulation
o High in
- Hypervoleamia
- CCF
o What it does (mostly opposite of ANII), all lead to decreased volume, CO, arterial BP.
- Decreases aldosterone released by adrenal
- Increases GFR
- Natriuresis and diuresis (K sparing
- Decreased renin and AN II release
o Chronically decreases SVR
- Vasodilation via, activation of guanylyl cyclase and vascular smooth muscle cGMP
- Attenuates sympathetic vascular tone by acting on CNS and inhibiting NE release
o NEP – neutral endopeptidase
- Enzyme that degradates ANP
- NEP inhibitors good in heart failure as increase ANP and this re inforces effect of ACE inhibitors
o BNP brain type natriuretic peptide – 32 amino acid peptide hormone related to ANP, released by ventricle when overloaded (heart failure), action like ANP
PO 1.47 factors that regulate and control BP
humoral control
can directly influence cardiac and vascular function or indirectly influence blood volume
antidiuretic hormone (vasopressin/AVP/ADH)
o release from posterior pituitary
o increases blood volume– increased preload and CO and BP
o acts on
- kidney
- increased water reabsorption by increasing permeability of collecting duct so get concentrate urine
- vessels
- constricts arteries at above physiological concentrations (only important in hypovoleamic shock)
o released by
- cardiopulmonary barorecetprs in atria, decreased firing when atrial pressure/CVP drops and hypotension, sends afferents to hypothalamus where AVP synthesized, transported via axons to posterior pituitary and secreted into circulation
- sympathetic activity from decreased baroreceptor activity in hypotension
- hyperosmolarity of dehydration sensed by hypothalamus so AVP released
- AN II receptors in hypothalamus stimulate release
o Paradoxically increased in heart failure
- Sympathetic and renin-angiotensis activation override low volume and pressure receptors
- Contributes to HTN and retention of fluid
