Vasoactive Peptides Flashcards
Vasoactive Peptides
Endogenous Angiotensin Kinins Endotheliuns Vasopressin Atrial natiuretic peptides Substance P
Function of Vasoactive Peptides
Play role in regulation of hemodynamics and its pathogensis
MoA
Act on cell surface receptors
Most via G protein receptors, cause production of second messengers
Some may open ion channels
Angiotensin
Renin acts on agniotensinogen, releasing angiotensin I and decapeptide
Angiotensin I is cleaved to II by angiotensin converting enzyme (ACE)
Active form of agniotensin
Angiotensin II
Causes vasoconstriction and other pharmacologic responses
Drugs that increase angiotensin
Cortiocosteroids
Estrogens
Thyroid hormones
Angiotensin II
ACE
Angiotensin converting enzyme
aka Peptidyl dipeptidase and Kininase II
Angiotensin I (decapeptide) to angiotensin II (octapeptide)
In vasculature and on luminal structur eod endothelial cells
Angiotensinase
Group of peptidases
Hydrolyze angiotensin II and angiotensin III into smaller inactive fragments
Pharmacologic Actions of Angiotensin II
Short half life
Regulation of vascular tone, fluid, electrolyte balance
Excessive production results in hypertension and disorders of hemodynamics
40 times more potent than norepi
Stimulates autonomic ganglion, increases release of EPI and NE from adrenal
Stimulates aldosterone production from adrenal
Glucocorticoid biosynthesis
Mitogenic agent for vascular and cardiovascular muscle cells, contribute to cardiac hypertrophy
Inhibitors of angiotensin
Drugs that block:
Renin secretion and action
Conversion of angiotensin I to angiotensin II
Angiotensin receptors
ACE Inhibitors
Block AT I to II
Inhibit degredation of bradykinin, substance P, and enkephaline
Hypotensive effect
Can cause cough, angioedema, and hypotensive shock
Angiotensin antagonists
Sarlasi,
Substitutes AA in AT II, AT II cannot form peptides
ARBs
Angiotensin Receptor Blockers
Losartan and Valsartan
Clinical benefits of ARBs and ACEi are almost the same
Bradykinins and kinins
Vasodilators
Produced by kallikreins or kininogenases
Kinins can be generated by insect bites
Bradykinin has opposite effect of angiotensin
Kinase II
Aka ACE
Digests Bradykinins
Kallikreins
Glycoprotein enzymes produced in the liver as prekallikreins
Present in:
Plasma
Kidney
Pancreas (this kallikrein can be activated by trypsin)
GI
Sweat glands
Salivary glands
In pancreatic cancer kallikreins can leak out and cause hypotension
Fletcher Factor
Prekallikrein
Promotes coagulation process via intrinsic system
Activated by factor XIIa (Hageman factor)
Kallikreins and DIC
Patient with consumption coagulapathy (DIC) develop hypotension due to increased kallikrein production
Kininogen
Protein substrates for kallikreins
LMWK (low)
HMWK (high)
Promotion of coagulation process in intrinsic pathway
Plasma kallikrein cleaves the HMWK to create bradykinin
Formation of kinins in Plasma and tissues
Bradykinin is released by plasma kallikrein
Found in plasma and urine
Actions of Kinins
Hemodynamic Effects
Vasodilation in several vascular beds:
Heart, liver, kidney, intestine, skeletal muscles, liver
10x more potent than histamine
Stimulate release of NO and PGE2 and PGI1
Promotes water and solution passage from blood to ECM (CAUSING EDEMA)
Actions of Kinins
Endo/exocrine gland
Kinins produced in the pancreas, kidney, glands may enter systemic circulation and cause hypotension
Actions of Kinins
Role in Inflammation and Pain
Kinins promote redness, local heat, swelling, and pain
Kinins are potent algesic agents
Produced pain by nociceptive afferents in skin and viscera
Kinin receptors
B1: predominant for mediation of biologic responses of kinins
B2: drugs that block bradykinin target these
