Regulation Of Vascular Smooth Muscle Flashcards by Emily Mosher

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

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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

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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)

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Autoregulation

. Intrinsic tendency of organ to main constant blood flow despite changes in arterial perfusion pressure

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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

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Tissues that have poor autoregulation

. Skin

. Lungs

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Tissues with good autoregulation

. Brain

. Kidneys

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2 major mechanisms responsible for dynamic autoregulation

. Myotonic and metabolic

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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

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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

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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

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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

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Local metabolic factors that are responsible for active vasodilation

. K 
. CO2
. local hypoxia 
. H+
. Phosphate ions 
. PGI2
. Adenine nucleotides 
. Adenosine

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Adenine nucleotides

. Have a receptor on endothelium 
. Inc. PGI2
. Inc. endothelial derived hyperpolarizing factor (EDHF)
. Inc. NO production 
. Promote relaxation

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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)

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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