Vasoactive Peptides

Question 1

Which vasoactive peptides are important vasoconstrictors?

Answer 1

• angiotensin II
• vasopressin
• endothelins
• neuropeptide Y

Question 2

Which vasoactive peptides are important vasodilators?

Answer 2

• bradykinin
• natriuretic peptides
• vasoactive intestinal peptide
• substance P
• neurotensin
• CGRP

Question 3

Describe biosynthesis of angiotensin II.

Answer 3

• angiotensinogen is synthesized in the liver
• renin is secreted in the kidneys and converts it to angiotensin I
• angiotensin I is converted to angiotensin II by ACE (angiotensin converting enzyme)

Question 4

Where is renin synthesized and stored?

Answer 4

in granular cells of the juxtaglomerular apparatus

Question 5

Renin secretion is increased in response to what?

Answer 5

• diminished NaCl flux through NKCC transporters in the macula densa
• B1 stimulation of granular cells
• low BP, which is sensed by baroreceptors in the afferent arteriole wall

Question 6

What are the primary actions of angiotensin II?

Answer 6

• increase peripheral resistance

- increase fluid volume

Question 7

What is the effect of ACE inhibitors on preload and afterload?

Answer 7

they decrease both preload and afterload

Question 8

Drugs ending in “-pril” belong to which class?

Answer 8

they are ACE inhibitors

Question 9

Through what three mechanisms do ACE inhibitors reduce BP?

Answer 9

• inhibit ATII-mediated vasoconstriction
• inhibit ATII-mediated release of aldosterone, which results in lowering blood volume
• inhibit ATII-mediated bradykinin breakdown, maintaining it’s vasodilative effect

Question 10

Why can ACE inhibitors lower BP even in those without elevated renin levels?

Answer 10

because it also serves to maintain elevated bradykinin levels, which has a vasodilative effect

Question 11

What are the three most significant adverse effects of ACE inhibitors?

Answer 11

• dry, hacking, non-productive cough
• angioedema or anaphylaxis (high bradykinin)
• hyperkalemia (low aldosterone)

Question 12

Which group of drugs have a signature side effect of dry, hacking, non-productive cough?

Answer 12

ACE inhibitors

Question 13

What group of drugs are named with the suffix “-sartan”?

Answer 13

angiotensin receptor antagonists

Question 14

How do angiotensin receptor antagonists compare to ACE inhibitors?

Answer 14

the angiotensin receptor antagonists don’t have the same effect on bradykinin metabolism, so they are less effective at reducing BP but also don’t cause cough or pose a risk for angioedema

Question 15

Aliskiren

Answer 15

the only renin inhibitor

Question 16

Bosentan

Answer 16

an endothelin receptor antagonist

Question 17

Aprepitant

Answer 17

a neurokinin-1 receptor antagonist developed as a potential analgesic but more useful in preventing chemotherapy-induced emesis

Question 18

Desmopressin

Answer 18

a vasopressin agonist with V2 selectivity

Question 19

Conivaptan

Answer 19

a vasopressin receptor antagonist

Question 20

How are kinins formed?

Answer 20

from kininogens by the action of kallikreins

Question 21

Most kinin biological effects are mediated by which receptor?

Answer 21

• most effects linked to B2

- B1 receptors have limited tissue distribution and function

Question 22

What are the inflammatory effects of kinins?

Answer 22

(all but fever)

• redness
• pain
• swelling
• heat

Question 23

Drugs ending in the suffix “-pressin” belong to which class of drugs?

Answer 23

they are vasopressin agonists

Question 24

What disease does a vasopressin deficiency cause?

Answer 24

diabetes insipidous

Question 25

What receptors are available for vasopressin? How do the effects and signal transduction mechanism of each differ?

Answer 25

• V1a have a vasoconstrictive effect mediated by Gq
• V1b induce ACTH release as mediated by Gs
• V2 have an anti-diuretic effect mediated by Gs

Question 26

What is the difference between desmopressin and vasopressin?

Answer 26

desmopressin has much greater V2 selectivity

Question 27

Desmopressin is used clinically primarily for what purpose?

Answer 27

the treatment of central diabetes insipidous

Question 28

Describe the activity of endothelins.

Answer 28

• they often act locally where a recent change in pressure or vessel dissension triggers release
• ETA receptors induce vasoconstriction, while ETB receptors trigger the release of EDRF (a vasodilator)
• they also have a direct positive inotropic and chronotropic effect on the heart
• the net result is a rapid and transient BP decrease followed by a prolonged increase in BP
• they also decrease glomerular filtration, increase secretion of renin and induce contraction of tracheal and bronchial smooth muscle

Question 29

CGRP is often co-localized with which other neurotransmitters?

Answer 29

• substance P

- acetylcholine

Question 30

The most potent vasodilator discovered so far is what?

Answer 30

CGRP

Question 31

What disease is thought to be mediated by CGRP?

Answer 31

CGRP released form trigeminal nerves is thought to produce migraines

Question 32

Neuropeptide Y is often co-localized with which other neutrotransmitter?

Answer 32

NE

Question 33

What are the effects of neuropeptide Y?

Answer 33

• increase feeding, hypotension, hypothermia, and respiratory depression in the CNS
• in the periphery it has a positive chronotropic and inotropic effect, but more importantly it causes vasoconstriction of cerebral blood vessels

Question 34

What is the importance of Y1 receptors?

Answer 34

they bind neuropeptide Y and are responsible for it’s vasoconstriction, inotropic, and chronotropic effects

Question 35

What is the importance of Y5 receptors?

Answer 35

they bind neuropeptide Y and control food intake

Question 36

Neuropeptide Y antagonists are being explored as possible medications for what?

Answer 36

• antihypertensives

- anti-obesity

Question 37

Many of the vasoactive peptides are inactivated by what class of enzyme?

Answer 37

endopeptidases

Question 38

Drugs ending in the suffix “-trilat” perform what function?

Answer 38

they inhibit ACE and neutral endopeptidase