What's an important vasoactive peptide that decreases BP?
How does it do so?
Short or long T1/2?
Atrial natriuretic peptide (ANP)
Diuretic, vasorelaxant
Short T1/2
Besides using NO donors, how else could impotence be treated?
Sildenfal (Viargra)
Which NO donor has an "ultrashort" duration of action (how long is this)?
Inhaled amyl nitrate
(3-5 minutes)
Name 5 important classes of vasoactive peptides in the body.
1. Angiotensins (I, II and III)
2. Bradykinin and related kinins
3. Vasopressin
4. Atrial natriuretic peptides and related peptides
5. Endothelins
______________ may be useful in impotence.
NO donors
Nitroglycerine ointment and nitroglycerine patches have been used.
Bosentin: MoA?
Endothelin receptor inhibitor
How is NO related to reperfusion?
lNO has been shown to protect against ischemic and reperfusion injury.
Pancreatic kallikrein can be activated by ___________.
trypsin
Describe the physiologic process that can generate endogenous nitric oxide.
*Generated from the oxidation of the guanidine group of arginine (L-arginine --> L-citrulline)
(Exposure to bacterial LPS result in the generation of NO in the macrophage.)
What are the actions of angiotensin II?
What dz can result if it's overproduced?
-
Exerts profound effects in the regulation of vascular tone, fluid and electrolyte balance.
-
It stimulates aldosterone production from the adrenal cortex.
-
At higher concentrations it produces glucocorticoid biosynthesis
Exerts profound effects in the regulation of vascular tone, fluid and electrolyte balance.
It stimulates aldosterone production from the adrenal cortex.
At higher concentrations it produces glucocorticoid biosynthesis
HTN & disorders of hemodynamics
Name (or read) some areas where prekallikreins are found. Where are they produced?
Kallikreins are glycoprotein enzymes produced in the liver as prekallikreins and are present in:
- plasma
- kidney
- pancreas
- gastrointestinal tract
- sweat glands
- salivary glands
Do the angiotensin antagonists have any effect on the actions on ACE?
No, only block receptor
What anti-inflammatory drug also has an effect on molecules generated by bradykinin? (explain, simply)
Aspirin is also known to block the algesic effects of prostaglandins generated by bradykinin.
What agents are useful during organ transplantation to preven accelerated graft atherosclerosis?
Nitric oxide acts as a cytoprotective agent and prevents cellular and platelet adhesion.
Dietary arginine supplements are helpful in the management of transplantation patients
What does angiotensinase do?
Inactivates ANG II and ANG III
What size of a peptide is ANG II?
ANG I?
*Octapeptide
Decapeptide
Desmopressin (DDAVP): MoA?
Vasopressin analogue
Desmopressin: indications?
Bleeding (restore factor VIII and vWF); control bleeding in minor surgeries.
(initially created for diabetes insipidus--vasopressin deficiency)
Explain in detail how NO affects platelets.
NO is a potent inhibitor of platelet adhesion, activation, aggregation, & regulates the release of 5-HT, growth factors, and TXA from platelets.
Platelets contain constitutive and inducible NOS's
Kinins represent one of the most potent groups of vasodilators peptides produced by the endogenous actions of enzymes known as ___________ or ___________.
kallikreins or kininogenases
Bosentin: route of administration?
PO
Pharmacologically, kinins stimulate the release of what 3 compounds?
Kinins promote water and solution passage from the blood to extracellular fluid resulting in __________.
NO, PGE2, and PGI2.
edema
How is the coagulation cascade related to kallikrein?
Factor XII (Hageman's factor) catalyzes the formation of kallikrein, which can go on to make bradykinin from HMW kininogen
Which NOS isoform is a/w chronic/acute inflammation?
NOS-3 (endothelial)
Recall: NO promotes edema + vascular permeability.
How does atherosclerosis affect NO?
What vascular effects does this lead to?
Impairs NO formation
results in vascular defects and increased cellular proliferation
Besides vasodilation, what other symptoms do kinins produce?
Kinins promote redness, local heat, swelling and pain (algesic).
What receptor subtypes can endothelins (ETs) bind?
ETA and ETB
What is the indication for ACE inhibitors? (captopril, enalapril)
HTN
Bradykinin is released by _________ kallikrein
plasma (not sure if important)
How big of a peptide is bradykinin?
What condition is it's overproduction a/w?
Nonapeptide
Hypotensive shock
