| hint |
answer |
| kinins |
peptide autacoids that act locally to cause pain, vasodilation, increased vascular permeability, and synthesis of prostaglandins. |
| initiates synthesis of kinins |
tissue damage, allergic reactions, acute and chronic infammation |
| 3 kinds of kinins |
bradykinin, kallidin, methionysl-lysylbradykinin |
| serine protease required for kinin synthesis |
kallikrens (exist as proenzyme "prekallikrein" until activated |
| substrate for kallikrein |
kininogens (either heavy-molecular-weight or low-molecular-weight) |
| formed by plasma kallikrein cleaving HMW-kininogen |
formed by tissue kallikrein cleaving LMW-kininogen |
| enzymes that metabolize kinins |
kinase I and kinase II (Angiotenisn Converting Enzyme; dipeptidyl carboxypeptidase) |
| half-life of kinins |
less than 15 seconds |
| receptors for kinins |
B1 and B2 |
| kinin receptor upregulated during inflammation and seems to be responsible for most of kinins inflammatory effects |
B1 |
| kinin recetor with high affinity for bradykinin |
B2 |
| kinin receptor coupled to a G-protein and activates phospholipase A2 and phospholipase C |
B2 |
| effects of kinins on arterial vascular beds |
vasodilation |
| mechanism of kinin effects on arterial vascular beds |
1. Direct 2. Indirect (mediated through EDRF and synthesis of PGE2 and PGI1) |
| effect of kinins of veins |
vasoconstriction, probably due to PGF2alpha production) |
| main effect of kinins on the cardiovascular system |
edema due to arteriole vasodilation, venous constriction, and contraction of epithelial cells |
| role of kinins in inflammation |
edema and bronchospasm in asthmatics |
| role of kinins in pain |
B2 receptors mediate acute pain while B1 recetors mediate chronic inflammation |
| effects of bradykinin on neonates |
dilation of fetal pulmonary artery, closure of the ductus arteriosis, and constricture of umbilical arteries |
| clinical uses of kinins |
no approved uses yet, but ACE inhibitors block kinase II, which causes kinin elevation and subsequent hypotensive action |
| potent vasoconstriction peptide |
angiotensis |
| first enzyme in the biosynthesis of angitoensin II |
renin |
| location of synthesis, storage, and release of renin |
juxtaglomerular cells of kidney |
| renin substrate |
angiotensiogen |
| site of angiotensiongen synthesis |
liver |
| converts angiotensin I to angiotensin II |
Angiotensin Converting Enzyme (ACE) |
| location of ACE |
luminal surface of vascular endothelial cells |
| synthesis pathway of Angiotensin II |
Angiotensinogen cleaved by renin->angiotensin I->converted to Angiotenisn II by ACE |
| rate-limiting factors for Angiotensin II production |
renin secretion and circulating angiotensin |
| comounds that increase concentrations of angiotensinogen |
corticosteroids, thryoid hormones, estrogen |
| provides negative feedback for the production of angiotensin |
vascular stretch receptors, sodium, alpha adrenergic tonus |
| postive feedback on angiotensin II production |
beta 1 adrenergic receptors |
| metabolism of angiotensin |
rapidly removed from blood |
| mechanism of angiotensin II action |
AT1 is a G-protein coupled receptor-->activate PLC-->IP3 and DAG-->smooth muscle contraction. Also increases NE release and decreases NE reuptake. Stimulates release of NE and E from adrenals |
| effect of angiotensin II on the cardiovascular system |
very potent vasoconstrictor (via smooth muscle contraction, and some CNS and ANS). Its effects on NE potentiate sympathetic transmission |
| effect of angiotensin II on the adrenal cortex, kidney, and CNS |
stimulates aldosterone and glucocorticoid biosynthesis, renal vasoconstriction, renal sodium reabsorption, stimulation of drinking response, vasopressin release (ADH), |
| clinical effect of renin inhibitors |
suppress angiotensin II production-->lower blood pressure in HTN patients |
| clinical effect of ACE inhibitors |
block conversion of Angiotensin I to Angiotensin II, as well as inhibiting metabolism of bradykinin. Overall effect is to maintain vasodilation and decrease blood pressure |
| ACE inhibiting drugs |
captopril (Capoten) and enalapril (Vasotec) |
| side-effect of ACE inhibitors |
cough due to build-up of kinins in lung and edema |
| conditions treated by ACE inhibitors |
hypertension and congestive heart failure |
| angiotensin II agonists that are orally active and have the useful effects of ACE inhibitors without the coughing and edema |
non-peptide Angiotensin II agonists (losartan, valsartan) |
| ubiquitous short-lived vasodilator |
NO (also known as Endothelium Derived Relaxing Factor) |
| 3 enzymes that produce NO |
cNOS(nNOS), iNOS, eNOS |
| constitutive NO enzyme present in neurons and epithelial cells |
cNOS (nNOS) |
| inducible NO enzyme present in macrophages and smooth muscle cells |
iNOS |
| constitutive NO enzyme present in endothelial cells |
eNOS |
| all three NOS isoforms are flavoproteins (T/F) |
True |
| substrate for NOS |
1-arginine |
| cofactors required for NOS isoforms |
NADPH, flavine adenine dinucleotide, tetrahydrobiopterin |
| products of NOS |
1-citrulline and NO |
| NO donors that spontaneously release NO |
nitroprusside, nitroglycerin |
| inactivate NO |
heme and superoxide (free radical) |
| increase potency and duration of NO |
antioxidants |
| product of glutathione interaction with NO |
S-nitrosoglutathione (long-lived carrier of NO) |
| NO mechanism |
activates soluble guanylyl cyclase-->produce cGMP-->activate protein kinase G-->smooth muscle relaxation |
| effects of NO on cardiovascular system |
maintenance of normal vascular tone |
| effect of NO inhibitors on cardiovascular system |
increase vascular tone, increase arterial pressure, potentiate vasopressor drugs. |
| effects of diabetes, atherosclerosis, and cardiac ischemia on NO |
decreased NO (and increased free radicals) |
| NO effect on LDL |
acts as an antioxidant to block its deposition on arterial walls (one of first steps in atherosclerosis) |
| NO effect on platelets |
decrease aggregation-->decrease chance of thrombus formation |
| NO effects on CNS |
diffusible second messenger that can facilitate the release of NTs-->potentiate developmental, learning, and memory functions |
| effect of excessive NO |
toxic to retinal neurons |
| type of neurons innervating the GI tract |
Non-adrenergic non-cholinergic (NANC) neurons that release NO |
| cause of penile erection |
NO release from NANC neruons-->increase cGMP-->relax smooth muscle-->allow blood influx-->erection |
| drug that potentiates NO-induced cGMP by inhibiting the phosphodiesterase that normally breaks down cGMP |
sildenafil (Viagra) |
| effect of NOS inhibitors on actue inflammation |
reduce edema and vascular permeability |
| effect of NOS inhibitors on arthritis |
reduce NO-induced COX2 activity-->decreased release of inflammatory prostaglandins |
| captopril (Capoten) drug type |
ACE inhibitor |
| enalapril (Vasotec) drug type |
ACE inhibitor |
| losartan (Cozaar) drug type |
AT1 receptor agonist |
| valsartan (Diovan) drug type |
AT1 receptor agonist |
| Nitroprusside drug type |
NO donor |
| Nitroglycerin drug type |
NO donor |
| sildenafil (Viagra) drug type |
selective inhibitor of the PDE that breaks down NO-dependent cGMP |
Ch.18 LTI-MA 509
