Vascular Signaling Pathways Flashcards
What does acute hyperemia mean?
When flow in a capillary bed is matched to metabolic demand of he tissue using local vasoactive metabolites
DIRECT LOCAL RESPONSE INDEPENDENT OF BLOOD PRESSURE
What are the vasoactive metabolites that control local flow to a capillary bed?
Decreased PO2
Increased PCO2 /decreased pH (incr lactic acid)
Increased K (with increased activity, the Na/K ATPase cannot keep up, so K accumulate in interstitial space)
Increased adenosine (product of ATP hydrolysis and functions through Gs inhibition of MLCK –> vasodilation)
What is the myogenic response
autoregulatory feedback to maintain constant flow in tissue despite changes in pressure (when you stand up)
what tissues exhibit myogenic response
vascular smooth muscle cells (vessels independent of endothelium)
what is the stepwise process of myogenic response countering blood pressure increase
1) increase pressure, increase flow (Q = P/R)
3) depolarization and increase intracellular Ca2+ via L-type Ca2+ channels
myogenic response
1) causes vasoconstriction to decrease flow
2) stretch activ ion channels in smooth muscle membrane that depol cell and direct Ca2+ entry (vasoconstriction)
What is NO
VASODILATOR ACTING AT LOCAL LEVEL
How is NO produced and why?
produced by endothelium to maintain basal vascular tone
Step process of NO activation
1) Humoral agents (ACh, bradykinin, etc) activate GPCRs on endothelial membrane
2) increase intracellular Ca2+
3) activates NO synthases –> produces NO
4) NO diffuses into vascular smooth muscle cells
5) NO activates guanylate cyclase, incr cGMP
6) cGMP activates PKG
7) PKG inhibits L-type Ca channels, decr Ca
8) relaxation of smooth muscles (VASODILATION)
What is endothelin
PEPTIDE VASOCONSTRICTOR to oppose NO
where is endothelin produced
produced by endothelium
what is the rate-limiting step in endothelin production?
endothelin converting enzyme (ECE)
which is inhibited by NO
what stimulates endothelin production and what inhibits?
stimulated by angiotensin, ADH, thrombin
inhibited by NO, ANP
step process of endothelin activation
1) endothelin binds ET receptors on vascular smooth muscle (receptor = GPCR coupled to Gq)
2) production of IP3, increase Ca2+ entry
3) contraction of muscle cells
How is endothelin response similar to alpha adrenergic response?
vasoconstriction via IP3 and increased Ca2+
BUT can also activate NO synthase (NO inhibits production of endothelin) so endothelin time course is SHORT
What is the primary system for long-term regulation of blood pressure?
renin-angiotensin-aldosterone system
What is renin?
Proteolytic enzyme released by renal juxtaglomerular cells
What stimulates release of renin?
1) sympathetic stimulation
2) decreased blood pressure in renal artery
3) decreased Na+ reabsorption
what is the fxn of renin?
cleaves inactive angiotensinogen to angiotensin I (AI) (also inactive)
What happens to angiotensin 1 (inactive)
Angiotensin I cleaved by Angiotensin Converting Enzyme to Angiotensin II (vasoconstrictor)
what is angiotensin II and what is its direct effect
VASOCONSTRICTOR by binding GPCRs on vascular smooth muscle
what are indirect effects of angiotensin II
stim sympathetic activity to induce
1) more vasoconstriction
2) aldosterone release
3) release of endothelin for more vasoconstriction
4) release anti-diuretic hormone from pituitary
what is aldosterone
steroid hormone made in adrenal cortex
what is fxn of aldosterone
1) incr reabsorption of Na and water in collecting ducts
–> INCR BLOOD VOLUME AND INCR BLOOD PRESSURE
what is anti-diuretic hormone aka ADH, Arginine Vasopressin
Peptide hormone formed in hypothalamus, released by pituitary
what stimulates release of ADH? (5 things)
1) hypovolemia
2) hypotension
3) high osomolarity
4) Angiotensin II
5) sympathetic stimulation
what is fxn of ADH?
binds receptors in kidney to incr water reabsorption
INCR BLOOD VOLUME AND BLOOD PRESSURE
bind receptors in vasculature–> vasoconstriction
myogenic response can be overcome by ____
vasoactive metabolites
____ can be overcome by vasoactive metabolites
myogenic response
what does NO being anti-atherogenic means?
decr NO, incr atherosclerosis
what is ANP
vasodilator peptide released by atria (mostly right)
ANP is releaed in response to what?
stretch of atria
function of ANP
long term regul of Na+ and water balance
incr GFR and secretion of Na+ and water
process of ANP action
1) ANP bind to natriuretic (sodium excr) peptide receptors
2) receptor guanylate cyclase incr cGMP
3) cGMP activ SERCA, incr Ca2+ uptake
Functions of ANP in vasculature
VASODILATOR (INHIB ENDOTHELIN)
function of ANP in adrenal gland
INHIB RELEASE OF ALDOSTERONE AND RENIN (incr secretion of Na+ and water)
what happens when you stand up? baroreceptor reflex
1) stand up
2) decr RA pressure, incr venous pressure in leg
blood pool in veins
3) incr hydrostatic pressure –> incr interstitial fluid, decr blood volume –> decr mean arterial pressure
4) baroreceptor reflex
5) incr symp outflow
6) decreased mean art pressure, decr firing rate of baroreceptor neuron
7) vasoconstrict smooth muscle b/c alpha adrenergic receptor –> MLCK
stand up
- myogenic response
1) stand up
2) decr RA pressure, incr venous pressure in leg
blood pool in veins
3) incr hydrostatic pressure –> incr interstitial fluid, decr blood volume –> decr mean arterial pressure
4) myogenic response
5) vasoconstriction and incr venous return to counter venous pool and decr in mean art pressure
stand up /exercise/hemorrhage
effect on heart
Heart = incr HR, incr CO, incr INOTROPY and LUSITROPY (new starling curve)
stand up /exercise/hemorrhage
effect on arterioles =
Arterioles = vasoconstrict, incr TPR –> restore mean arterial pressure
stand up/exercise/hemorrhage
effect on veins
veins = incr venous constriction, incr venous retrun
Exercise
central command effect
1) exercise
2) incr symp tone
3) decr parasymp tone
Exercise
local responses effect
1) exercise
2) incr vasoactive metabolites
3) vasodilation in exercising muscle
4) incr flow via Poiseuille Q~ r^4
5) activity of skeletal muscle incr venous return, incr interstitial P, incr SV (Starlings)
effect of hemorrhage (renin system)
1) hemorrhage
2) decr mean arterial pressure b/c blood leak out
3) incr renin
4) incr angiotensin II
5) incr aldosterone and total periph resistance
6) incr Na+ reabsorption/H2O
7) incr blood volume
effect of hemorrhage in capillaries
1) hemorrhage
2) decr mean arterial pressure b/c blood leak out
3) decr capillary hydrostat pressure
4) incr capill reabso
5) incr blood volume
