Vascular Signaling Pathways

Question 1

What does acute hyperemia mean?

Answer 1

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

Question 2

What are the vasoactive metabolites that control local flow to a capillary bed?

Answer 2

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)

Question 3

What is the myogenic response

Answer 3

autoregulatory feedback to maintain constant flow in tissue despite changes in pressure (when you stand up)

Question 4

what tissues exhibit myogenic response

Answer 4

vascular smooth muscle cells (vessels independent of endothelium)

Question 5

what is the stepwise process of myogenic response countering blood pressure increase

Answer 5

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)

Question 6

What is NO

Answer 6

VASODILATOR ACTING AT LOCAL LEVEL

Question 7

How is NO produced and why?

Answer 7

produced by endothelium to maintain basal vascular tone

Question 8

Step process of NO activation

Answer 8

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)

Question 9

What is endothelin

Answer 9

PEPTIDE VASOCONSTRICTOR to oppose NO

Question 10

where is endothelin produced

Answer 10

produced by endothelium

Question 11

what is the rate-limiting step in endothelin production?

Answer 11

endothelin converting enzyme (ECE)

which is inhibited by NO

Question 12

what stimulates endothelin production and what inhibits?

Answer 12

stimulated by angiotensin, ADH, thrombin

inhibited by NO, ANP

Question 13

step process of endothelin activation

Answer 13

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

Question 14

How is endothelin response similar to alpha adrenergic response?

Answer 14

vasoconstriction via IP3 and increased Ca2+

BUT can also activate NO synthase (NO inhibits production of endothelin) so endothelin time course is SHORT

Question 15

What is the primary system for long-term regulation of blood pressure?

Answer 15

renin-angiotensin-aldosterone system

Question 16

What is renin?

Answer 16

Proteolytic enzyme released by renal juxtaglomerular cells

Question 17

What stimulates release of renin?

Answer 17

1) sympathetic stimulation
2) decreased blood pressure in renal artery
3) decreased Na+ reabsorption

Question 18

what is the fxn of renin?

Answer 18

cleaves inactive angiotensinogen to angiotensin I (AI) (also inactive)

Question 19

What happens to angiotensin 1 (inactive)

Answer 19

Angiotensin I cleaved by Angiotensin Converting Enzyme to Angiotensin II (vasoconstrictor)

Question 20

what is angiotensin II and what is its direct effect

Answer 20

VASOCONSTRICTOR by binding GPCRs on vascular smooth muscle

Question 21

what are indirect effects of angiotensin II

Answer 21

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

Question 22

what is aldosterone

Answer 22

steroid hormone made in adrenal cortex

Question 23

what is fxn of aldosterone

Answer 23

1) incr reabsorption of Na and water in collecting ducts

–> INCR BLOOD VOLUME AND INCR BLOOD PRESSURE

Question 24

what is anti-diuretic hormone aka ADH, Arginine Vasopressin

Answer 24

Peptide hormone formed in hypothalamus, released by pituitary

Question 25

what stimulates release of ADH? (5 things)

Answer 25

1) hypovolemia
2) hypotension
3) high osomolarity
4) Angiotensin II
5) sympathetic stimulation

Question 26

what is fxn of ADH?

Answer 26

binds receptors in kidney to incr water reabsorption
INCR BLOOD VOLUME AND BLOOD PRESSURE

bind receptors in vasculature–> vasoconstriction

Question 27

myogenic response can be overcome by ____

Answer 27

vasoactive metabolites

Question 28

____ can be overcome by vasoactive metabolites

Answer 28

myogenic response

Question 29

what does NO being anti-atherogenic means?

Answer 29

decr NO, incr atherosclerosis

Question 30

what is ANP

Answer 30

vasodilator peptide released by atria (mostly right)

Question 31

ANP is releaed in response to what?

Answer 31

stretch of atria

Question 32

function of ANP

Answer 32

long term regul of Na+ and water balance

incr GFR and secretion of Na+ and water

Question 33

process of ANP action

Answer 33

1) ANP bind to natriuretic (sodium excr) peptide receptors
2) receptor guanylate cyclase incr cGMP
3) cGMP activ SERCA, incr Ca2+ uptake

Question 34

Functions of ANP in vasculature

Answer 34

VASODILATOR (INHIB ENDOTHELIN)

Question 35

function of ANP in adrenal gland

Answer 35

INHIB RELEASE OF ALDOSTERONE AND RENIN (incr secretion of Na+ and water)

Question 36

what happens when you stand up? baroreceptor reflex

Answer 36

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

Question 37

stand up

- myogenic response

Answer 37

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

Question 38

stand up /exercise/hemorrhage

effect on heart

Answer 38

Heart = incr HR, incr CO, incr INOTROPY and LUSITROPY (new starling curve)

Question 39

stand up /exercise/hemorrhage

effect on arterioles =

Answer 39

Arterioles = vasoconstrict, incr TPR –> restore mean arterial pressure

Question 40

stand up/exercise/hemorrhage

effect on veins

Answer 40

veins = incr venous constriction, incr venous retrun

Question 41

Exercise

central command effect

Answer 41

1) exercise
2) incr symp tone
3) decr parasymp tone

Question 42

Exercise

local responses effect

Answer 42

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)

Question 43

effect of hemorrhage (renin system)

Answer 43

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

Question 44

effect of hemorrhage in capillaries

Answer 44

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