vasoactive peptides Flashcards
what are vasoactive peptides
autocoids(act like local homrone, have a brief duration, and act near their sites of biosynthesis)with significant actions on vascular smooth muscles as well as other tissues
— include vasoconstriction, vasodilations, and peptides with missed effects
sometimes secretor cells, secret peptides that resule in action of adjacent cells
what is vasopressin and their effect at different concentrations
shares a dual physiologial effect of vasoconstriction(pressor) and antidiuresis(volume) thus also know as antidiuretic hormone
at low conco only have antidiuresis effect
released by posterior pituitary in response to falling blood pressure on rising plasma tonicity(reducing in blood volume)
- important role in long term control of blood pressure regualtionof arterial pressure by its vasoconstriction actions
what is angiotensin
potent vasoactive hormone, important in blood pressure homeostasis
there are AT1,2,3
AT 2 is the most active
they are present in circulation
-synthesisde from protein precusrosr called angiotensiongen by the action of resin, whci is released from the kidney
what are facros that affec the blood pressure
cardia output :: heart rate, contractility, (blood volume and venous return)(filling pressure)
and
peripheral resistance: arteriolar tone
what is pre load and after load
pre load is the stretching of cardia muscles before contraction, associated with ventricular filling
after load is the force against which the heart has to contract to effect the blood , associated with peripheral resistance
flow relationship with difference in the pressure between 2 points AND resistance
directly proportional and inversly proportional to the resistance
list the formation of AT and the enzyme needed for each AT
ATensinogen TO 1: renin
at1-at2: ACE
2-3: aminopeptidase A
3-4: aminopeptidase N
what is the emchanism of action of ATII receptors
ATII receptors are ATSMALL1 AND ATSMALL2
ATSMALL1- are g protein receptors coupled to many transduciton pathways,
phospholipase CIP3/DAG pathway, tyrosine phsophorylation pathways(JAK/STAT) and mediate most known action at AT - vasoconstriction
ATSMALL2 - GPCR, functional roles are not clearly established
what are actions that happen after ANGIOTENSIN II is formed
vasoconstrition that caused blood pressure to increase
aldosteron sectreion that results in the NA retention and rise in blood volume and rise in blood pressure
factors that decrease renin relase
blood pressure rise
blood volumen rise
na retention
factors that increase renin release
blood pressure decrease
blood volume fall
na depltetion
what are the effect of angiotensin renin on cardiovascular system
increase blood pressure
- this increase is more than noradrelaine
rapid onset when given in iv
acts mainly by contracting the arteriolar smooth muscles
central action on are of the postrema in the medulla, oblongata to increase sympathetic discharge and to reduce vagal tone to the heart
-reset baroreflec to a higher pressure
- facilitates sympathetic transmission by increasing release and reducing uptake of noradrenaline
what are the effect of angiotensin renin on adrenal glands
increaes the adrenaline release from the adrenal medulla
- stimulaets aldostrone secretion in the adrenal cortex
- renin angiotensin system is a major regulator of aldosterone secretion
what are the effect of angiotensin renin on kidney
causes renal vasoconstriction
increases na+ absorbtion in the proximal tubules
inhibits renin secretion
what are the effect of angiotensin renin on the central nervous system
action on the area postrema leading to increase in blood pressure
- stimulates drinking(dipogenic effect)
increase secretion of vasopressin and adrenocricotrophic hormone(ACTH)
list the clinial use of angiotensin
given by slow iv infusion
- only limited use as an alternative to sympathomimetic amine
- pressor effect well sustained and unlikely to be accompanied by cardiac arrhythmia
– suitable for hypertensive crisis during anaesthesia when the use of astecholamine may cause cardia arrhythmia
what are the ways to antagnoise ATII
- angiotensin converting enzyme inhibitor
- angiotesin receptor antagonist
3.renin inhibitor
list the angiotensin converting enzyme inhibitor
captopril
enalopril
lisinopril
angiotenin receptor antagnoist
saralsin, losartan, valsartan, candesartan
renin inhibitor
aliskiren
what are the effects of ACE inhibiton
decrease ACE
prevent inhibition of brandykinin
thus increase in NO and PG
vasodilation
thus decrease in blood pressure
therapeutic use of ACE inhibitors
- hypertension
maximal lowering og blood pressure may take several week sto develop
when used alone, lower blood pressure significantly in abt 50% of patients with moderate essential hypertension, comparable to thiazide diuretics, or b blocker - chrnoic congestive heart failure
induce arterolar dilation, thereby reducing afterload
induce venodilations, reducing preload
thus increase cardiac output, reduce signs and symptoms of congestion, increase exercise tolerance
ATII ATSMALL1 antagonist what does it do
the sartans= angiotensin receptor blockers
- non peptide, potent and specific antagonist against ATII action on ATSMALL1 receptors
- orally active with no agnoist activity
- treatment of hypertension with similar effectiveness to ACE inhibitor but lower incidence of cough
- also alternative to ACE inhibitor in treatment of heart failure
—- contraindication: pregnancy
renin inhibior
first non peptide, orally active renin inhibitor approved for treatment of hypertension, effective as monotherapy
– long duration of action lasting up to 4 weeks after therpahy is stopped
- combined with other antihypertensive resulting in greater therapeutics efficacy without adverse drug interactions
what are vasopressin route of action
mediate thur the receptors of vasopressin
receptors
v1 receptors found in smooth muscles cells and mdeicate vasoconstriction
v2 receptors: found in renal tubules cells and mediate antidiuresis thruogh increased water permeability and water absorption
v2 receptors found outside the kidnes mediate the release of coagulation factor VIII and von willebrand factor
what are the vasopressin receptor agonist
vasopressin - weak selectivity, short duration, injected im or iv
selepressin: v1 selective, being developed for us in septic shock
desmopressin : v2 selective, longer duration of action, nasal spray
clincial use of vasopressin receptor agonisyt
ADH sensitve diabetes insipidus
- provides effective and immediate therapy with reduction of urine volume to normal
- desmopressin, drug of choice
- bc 12 times more potent and no pressor effect
can be administered intransally rather than injection(therapy is life long)
- longer plasma half life than vasopressin
- may also be used to treat persistent nocturnal enursis in older children and adults
list the vasopressin antagonist
conivaptan
- non selective
-approved ofr treatment of hypoantremia caused by syndrome of inappropriate adh(SIADH)
tolvaptan
- 30 fold higher affinity for v2 than v1
- approved for treatment of hyponatremai associated with congestive heart failure and SIADH
