Vascular Physiology 2 Flashcards
effects of the parasympathetic nervous system on the CV system
*parasympathetic nervous system responds chiefly when there is an INCREASE in BLOOD PRSSURE
*the increased blood pressure causes more nerve impulses
*the CNS inhibits the sympathetic system and increases signals down the vagus nerve
*parasympathetic system decreases heart rate by slowing automaticity and slowing the conduction velocity through the AV node (decreased dromotropy)
M2 acetylcholine receptor → decreased CO by lowering heart rate
*the binding of ACh to muscarinic receptors decreases automaticity (→ chronotropy) and decreases dromotropy
*by decreasing CO through lowering the heart rate, the parasympathetic system through the muscarinic receptor activated by the vagus nerve hopes to decrease blood pressure
*note that the arterioles cannot be directly stimulated by the parasympathetic nervous system
atrial stretch receptors
*a decrease in atrial stretch (i.e. volume depletion) results in increased RAS activity and increased vasopressin
*an INCREASE in atrial stretch results in release of atrial natriuretic peptide (ANP)
ventricular tension receptors
*an increase in ventricular stretch/tension results in release of B-type (Brain) natriuretic peptide (BNP)
*has similar action as ANP except BNP lasts longer
BNP and ANP - overview
*BNP: B-type (brain) natriuretic peptide
*ANP: atrial natriuretic peptide
*act at several sites:
1) renal:
-get rid of sodium and fluid through urine
-inhibits renin release
2) adrenal:
-inhibits aldosterone release
3) heart:
-prevents maladaptive hypertrophy
4) blood vessels:
-relaxes both arterial and venous tone
*net results: DECREASED PRELOAD & DECREASED AFTERLOAD
natriuretic peptide receptor
*leads to vasodilation through activation of guanylyl cyclase → INCREASED cGMP
*natriuretic peptides are broken down by the enzyme Neprilysin
*several different types of ANP/BNP receptors
cyclic GMP - overview
*inhibits Ca2+ influx into cell
*hyperpolarizes the cell
*stimulates myosin light-chain phosphatase to break myosin-actin bonds (decrease vasoconstriction)
systemic vs. local vascular control
*by vasoconstricting, the sympathetic system preferentially shifts flow to those areas where the metabolism causes vasodilation
*by raising blood pressure, you further increase the flow to those areas which are vasodilated due to metabolic need
*with sympathetic activation, beta-2 increases blood flow to liver (increase glucose and triglyceride availability) and skeletal muscle to support “fight or flight” response
vascular tone
*a general term used to denote the general contractile state of a vessel or a vascular region
*an increase in arteriolar tone is automatically taken to mean a decrease in arteriolar vessel diameter, which increases arteriolar resistance and decreases flow
*basal tone in the arterioles is a critical factor for determining SVR
myogenic response
*as transmural pressure increases, arterioles respond both passively and actively:
-an increase in internal pressure results in mechanical dilation
-followed by a mechanical constriction, which may completely reverse the initial distention
*the opposite occurs when there is a decrease in internal pressure
autoregulation of blood flow
*an abrupt increase in blood pressure is normally accompanied by an initial increase in organ blood flow, which then gradually returns toward normal, in spite of elevated blood pressure
*the subsequent return of FLOW to normal levels is caused by a gradual INCREASE in active ARTERIOLAR TONE (constriction), which INCREASES RESISTANCE to blood flow
*ultimately, a new steady-state is reached with only slightly increased blood flow
*PURPOSE: to maintain a CONSTANT FLOW OF BLOOD, regardless of what the blood pressure is
local metabolic influences on arteriolar tone: OXYGEN
*as oxygen saturation decreases, the blood flow INCREASES (EXCEPT in the pulmonary arteries)
*in systemic vascular beds, a vascular region starved for oxygen causes VASODILATION of the arteriole
*this vasodilation of the “feeding” arteriole lowers the resistance, which increases blood flow to this area in need of more oxygen
local metabolic influences on arteriolar tone: METABOLITES
*as the rate of metabolism in a particular organ increases, the blood flow to that organ increases to meet the needs
*as metabolism increases, the tissue levels of certain ions and products of metabolism change:
-increased CO2, H+ (more acidic), K+, ADP, adenosine
*as these levels change, the arterioles dilate to provide more oxygen to this area and remove products of metabolism
adenosine & adenosine receptor
*adenosine is a very powerful VASODILATOR
*as metabolism increases, adenosine gets released → vasodilation
*A2A is the adenosine receptor:
-increases cAMP by Gs protein signaling, which then inhibits the myosin light chain kinase, which ultimately prevents myosin-actin cross-bridge formation
*DECREASES VASCULAR RESISTANCE (vasodilation)
hyperemia
*hyperemia (HIGH FLOW) is the phenomenon of increased organ blood flow to increased products of metabolism
*active hyperemia is in response to local metabolic vasodilator feedback on an arteriolar smooth muscle as a result of increased metabolic rate
*REACTIVE hyperemia is in response to a transient period of arrested flow
vascular endothelium - overview
*single cell forming a barrier between blood and vascular smooth muscle
*produces and secretes multiple factors that can modify the tone and function of the underlying smooth muscle
vascular endothelium & vascular tone
*in response to sheer stress or certain substances (Ach, substance P, bradykinin, vasoactive intestinal peptide) which can activate a receptor, the endothelial cell uses oxygen and L-arginine to produce nitric oxide and L-citrulline
*nitric oxide diffuses through the underlying endothelium, where is activates a soluble form of guanylate cyclase, which converts cGTP → gGMP
*RELAXATION OF VASCULAR SMOOTH MUSCLE
endothelial dysfunction as a manifestation of vascular injury
*when endothelial cells are damaged by chronic HTN or atherosclerosis, impaired NO synthesis causes excessive vasoconstriction
*this worsens the HTN and endothelial damage, which may further vascular injury (vicious cycle)
acetylcholine and blood vessel reactivity
*if endothelium is normal, ACh causes VASODILATION
*if endothelium is dysfunctional/damaged, ACh causes VASOCONSTRICTION by inducing smooth muscles to contract
Cushing reflex
*as intra-cranial pressure increases (due to a bleed), it reduces the amount of blood flow to the brain
*to compensate, the systolic BP and pulse pressure rise to try to overcome the increased intra-cranial pressure (mediated by sympathetic nervous system)
*meanwhile, baroreceptors in the aortic arch detect the increase in BP and trigger a parasympathetic response via the vagus nerve → bradycardia
*CUSHING’S TRIAD: irregular respirations, increased systolic BP, and bradycardia
diving reflex
1) bradycardia = immediate response to submersion
2) peripheral vasoconstriction: to conserve blood flow/warmth for torso/brain
vasovagal syncope
*caused by inappropriate carotid baroreceptor activation → increased vagal tone w/ decreased sympathetic tone → hypotension +/- bradycardia → syncope (passing out)
orthostatic hypotension
*defined by a drop in SBP > 20 or DBP > 10 mmHg
*often can also be tachycardic
*can be caused by pooling of blood in legs on standing
*dehydration
coronary blood flow - overview
*in resting individual, the myocardium extract 70-75% of the oxygen in the blood, which means that it cannot extract more oxygen to meet increased needs
*increased myocardial oxygen consumption is met by INCREASED CORONARY BLOOD FLOW, which is controlled by local metabolites
*while sympathetic stimulation drives an increase in myocardial oxygen demand through beta-1, the LOCAL METABOLIC NEEDS OVERRULE THE alpha-1 receptors (vasoconstriction) to cause VASODILATION
right coronary vs. left coronary flow
*in the left coronary, the coronary capillaries and small arteries are being squeezed during systole (so there is little flow), but there is increased flow during DIASOTLE
*in the right coronary, you have blood flow in both systole and diastole
blood flow to the LV endocardium
*b/c the arteries to the LV endocardium travel through the heart muscle, they are more susceptible to no blood flow from the systolic compressional forces that occur during systole
*epicardial flow > endocardial flow
*normally, the endocardium can make up the lack of flow during systole via high flow during diastole
*b/c the endocardium is the most susceptible to lack of blood flow, it is the section of the wall which will be hit hardest from a blocked artery and have a MI
coronary artery stenosis & blood flow
*blood flow in coronary arteries is not limited until a stenosis is GREATER THAN 70%
*the coronary arteries are able to maintain adequate blood flow if the stenosis is < 70%
vascularity
*long-term control of blood flow is related to vascularity
*if the metabolism of a tissue increases long-term, the increased metabolic need is met with more blood flow by creating new arteries (angiogenesis)
*in oxygen-deprived environments, there is an increase in vascularity to help distribute what oxygen there is
*in oxygen-rich environments, new blood vessel growth is inhibited
*while young, vascularity increases quickly, but as we age, it can take months
*INCREASED VASCULARITY is driven more by MAXIMUM DEMAND than average demand (hence, exercise results in increased vascularity)
new blood vessel growth (angiogenesis) - overview
*tissues which need oxygen release vascular endothelial growth factor (VEGF)
*first, the BM of the endothelium dissolves, and endothelial cells grow towards VEGF
*as blood flow increases, vascular smooth muscle cells follow along with the endothelial cells
*eventually, they will develop into arterioles, capillaries, and veins for the areas in need of oxygen (forming collateral circulation)
inhibitors of new blood vessel growth
*several factors have been found which impair the ability to make new blood vessels:
-steroids
-endostatin
-angiostatin
*inhibition of angiogenesis presents a unique and compelling mechanism to limit tumor growth
