Regulation Of Vascular Smooth Muscle Flashcards
Local control of blood flow to vascular bed controls what aspects of tissue needs?
. Delivery of O2
. Delivery of nutrients to tissue
. Removal of CO2 from tissues
. Removal of H from tissues
. Maintenance of proper concentrations of other ions in the tissues
. Transport of hormones and other substance to tissues
The largest pressure drop in circulatory system occurs along ____
Small arterioles and precapillary sphincters
. Due to large number of capillary vessels arranged in parallel dec. their resistance
Functions of local blow flow control mechanisms
. Maintaining tissue blood flow at constant level
. Match blood flow to metabolic needs of tissue (inc. metabolism, inc. blood flow)
Autoregulation
. Intrinsic tendency of organ to main constant blood flow despite changes in arterial perfusion pressure
Autoregulation in local blood flow when arterial pressure inc.
. Passive, rapid inc. in blood flow followed by gradual decline towards initial value
. Blood flow dec. due to automatic change in resistance (vasoconstriction)
. Results in autoregulation of vascular bed
Tissues that have poor autoregulation
. Skin
. Lungs
Tissues with good autoregulation
. Brain
. Kidneys
2 major mechanisms responsible for dynamic autoregulation
. Myotonic and metabolic
Myogenic response in autoregulation
. Smooth muscle-active response to acute changes in transmural pressure
. If pressure dec., smooth mm. Relax,opposite if pressure inc.
. Results in gradual return of blood flow at initial level
. Stretch-sensitive ion channels involved
. Dec. in perfusion pressure causes passive dec. in vessel diameter (passive dec. in wall tension) and blood flow -> smooth mm. Relaxes -> diameter inc. -> resistance dec. -> blood flow returns to initial level
. Opposite for inc. in perfusion pressure
Metabolic regulation of blood flow
. Passive changes in blood flow caused by change in perfusion pressure affect local conc. Of vasodilator metabolites
. Present at any given cell activity level, but influence depends on conc.
. If pressure inc., flow inc. -> inc. flow washes out the local conc. Of metabolites and smooth mm. Constricts -> returns to initial blood flow
. Opposite for dec. in pressure
. Tissue metabolism is not changing under these conditions
Blood flow in active hyperemia
.blood flow of organ locally adjusted to meet the inc. metabolic demands of tissue
. As rate of metabolism inc., blood flow inc. due to inc. production of vasodilator metabolites
. Important mechanisms for raising blood flow in response to skeletal mm. Activity and inc. work in cardiac, GI, and cerebral tissues
Blood flow in reactive hyperemia
. In response to ischemia, blood flow inc. above initial levels after release of occlusion
. Accumulation of metabolites during ischemia drives dilation of vessels
. Hyperemia gradually resolves as blood flow washes out metabolites accumulated
. Duration and magnitude of hyperemia is proportional to time of ischemia
Local metabolic factors that are responsible for active vasodilation
. K . CO2 . local hypoxia . H+ . Phosphate ions . PGI2 . Adenine nucleotides . Adenosine
Adenine nucleotides
. Have a receptor on endothelium . Inc. PGI2 . Inc. endothelial derived hyperpolarizing factor (EDHF) . Inc. NO production . Promote relaxation
Adenosine
. Purine nucleoside released from cells when metabolism inc. or hypoxia
. Causes vasodilation by acting directly on vascular smooth mm. To inc. cAMP production (adenosine A2 receptor) and/or stimulating NO release of NO from vascular endothelial cells (adenosine A1 receptor)
Sympathetic control of vascular tone
. Controls vascular resistance in most vascular beds
. Precapillary resistance vessels innervated via postganglionic nn. That use NE
. Fibers tonically active in most beds so withdrawal of sympathetic causes passive vasodilation
. Contraction is mediated via a1 adrenergic receptors on smooth mm.
. Constriction may be attenuated by local vasodilator metabolites or mediators
Parasympathetic control of vascular tone
. Arterioles in mist vascular beds don’t have PNS innervation
. Exception: external genitalia, cerebral, and coronary tissues
. Vasodilation mediated via muscarinic receptors that trigger NO generation
. Vasodilation of these small vascular beds does not directly affect systemic vascular resistance
Endothelial based control of smooth muscle tone
. Endothelium itself can release vasoconstrictors and vasodilators in response to mechanical forces, local metabolites, NTs, hormones, and peptides
. Flow induced arterial vasodilation: endothelial-based dilation mediated by NO causing acute inc. in blood flow
Vasodilator substances generated in endothelial cells that control vascular tone
. NO released in response to shear stress, NTs like ACh, bradykinin, histamine, serotonin, and ATP/ADP ratio
. All factories inc. intracellular Ca that activates NO synthase (NOS) to generate NO from Arg
NO pathway
. Diffuses into vascular smooth mm. -> activates guanylyl cyclase-> inc. intracellular cGMP conc. Promoting relaxation of smooth mm.
Phosphodiesterase inhibitor
. Phosphodiesterase breaks down cAMP and cGMP
. Inhibitor prevents this causing continued vasodilation
. Viagra in example (ED and pulmonary hypertension treatment)
Endothelium-derived hyperpolarizing Factor
. Hyperpolarizing smooth mm. Causing relaxation
. Triggers K efflux from smooth muscle cells
. Interstitial K is known to open certain K channels
. Other putative factors include H2O2 and short-lived products of arachidonic acid cascade (EETs)
Prostacyclin (PGI2)
. Family of substances that are generated from arachidonic acid in cell membranes using the COX pathway
. Inhibition of COX enzyme is main pharmacological effect of NSAIDs
. Some are vasodilatory and vasoconstrictors
. PG family and related compounds are involved in inflammation
. PGI2 released from endothelial cells and other tissues
. Released by many of the same factors that cause NO release
. Acts at a receptor vascular smooth m. To inc. cAMP promoting relaxation
. Inhibits platelet aggregation
Histamine
. Biologically active amine
. Released from mast cells
. Relaxes arterioles and precapillary sphincters and inc. capillary permeability (Kf)
. Promotes relaxation by acting on H2 receptors on vascular smooth m. To inc. cAMP promoting relaxation OR
. Acting on H1 receptors on endothelial cells to promote NO production and stimulate PGI2 release from endothelium
Serotonin
. Biologically active amine
. Released from platelets
. Vasodilator responsemediated by endothelial release of NO
. In absence of intact endothelium, it directly constricts vascular smooth mm. Of arterioles
. Also constricts postcapillary venules
Bradykinin
, local peptide
. Arteriolar vasodilation mediated by endothelial release of NO, PGI2, and EDRF
. Caused inc. venule permeability leading to inc. filtration
Atrial natriuretic peptide (ANP)/B-type natriuretic peptide (BNP)
. Family of peptide hormones synthesized and stored in atrial (ANP) or ventricular (BNP) myocytes
. Released w/ atrial stretch (ANP) or ventricular pressure/volume overload (BNP)
. Vasodilator action results form stimulation of guanylyl cyclase activity in vascular smooth m. (NPR-A and B receptors)
. ANP acts directly on smooth mm. To promote relaxation
. Promotes natriuresis and diuresis and inhibits myocardial hypertrophy and fibrosis
. Inhibits renin release and aldosterone synthesis and release
Neutral endopeptidase (NEP)
. Neprilysin
. Breaks down natriuretic peptides
. NEP inhibition is potential therapeutic strategy in chronic HF
. Catalyzes the degradation of angiotensin II ad bradykinin
Endothelin
Family of related peptides
. Released in response to stretching of blood vessels and other hormones (catecholamiens/AII)
. Important under pathophysiologic conditions
. Vasoconstriction mediated by ETa receptors on vascular smooth mm. Causing inc. Ca release from SR
. Vasodilation occurs through ETb receptors and buffers vasoconstriction produced by ETA receptors
. Net effect is vasoconstriction
Prostaglandins
Arachidonic acid derivatives generated in endothelial cells
. PGH2 may act directly as a vasoconstrictor or be source of synthesis of TxA2
. Synthesis of vasoconstrictors vs vasodilators from PGH2 depends on secondary enzymes
. PGF2alpha: vasoconstrictor in circulatory beds and causes contraction of uterine smooth muscle
. TXA2: structurally related to PG, produced by aggregating platelets, act directly on smooth m. To cause vasoconstriction
Epinephrine
. Released from adrenal medulla from SNS activation
. Contraction via alpha1/2 adrenergic receptors on vascular smooth mm. Of resistance vessels and veins
. Relaxation of beta2 adrenergic receptors on vascular smooth m. Of resistance vessels
. Net effect dependent on conc. In plasma, density of adrenergic receptors, and affinity of E to adrenergic receptors in that tissue
. Most tissues vasocontriction
. Skeletal mm. Have vasodilation due to higher conc. Of beta2 receptors and higher E affinity
Angiotensin II
. Peptide hormone produced from sequential hydrolysis of precursor angiotensinogen
. Released in response to low bp and low blood volume
. Potent vasoconstrictor
. Acts directly on vascular smooth m. Of resistance vessels and endothelium by AT1 receptor
Vasopressin
. Peptide hormone released from post. Pituitary in response to rising plasma osmolality or falling bp or AII
. Potent vasoconstrictor
. Acts directly on vascular smooth m. (V1 receptors/V1R) of resistance vessels
