Local Blood Flow Regulation Flashcards
dense bodies
structures that actin filaments attach to in smooth muscle cells in the interior of the cell
correlates to the Z-line
dense bands
structures where actin filaments attach to the inner surface of the cell
latched state
the state of contraction in smooth muscle that can be maintained by low energy consumption
probably involves very slow cycling or even non-recycling cross-bridges
regulation of smooth muscle contractile activity
changes in intracellular free calcium levels
changes in calcium sensitivity of the contractile machinery
calcium release from the SR in smooth muscle
voltage operated calcium channels
receptor operated calcium channels
chemical activation (IP3) of calcium release calcium binds with calmodulin to activate myosin light chian kinase, promoting contraction
mechanisms for smooth muscle contraction
protein kinase C linked receptors
coupled via a G protein to phospholipase C
IP3 causes calcium release from SR
DAG activates PKC
mechanisms for smooth muscle relaxation
calcium is pumped back into the SR
nitric oxide generated cGMP inhibits myosin kinase and promotes relaxation
factors regulating vascular smooth muscle contraction
activity of symathetic nerves
agents produced and/or secreted by the endothelium
factors in circulation such as hormones, catecholamines, blood gases
renin-angiotensin system
angiotensin -> angiotensin I (through renin) -> angiotensin II (through ACE)
angiotensin II receptors are of the AT1 subtype
leads to vasoconstriction and aldosterone release
autoregulation
process by which a change in the perfusion pressure is countered by a change in resistance in the vascular bed that kepes flow relatively constant
theories for mechanisms of autoregulation
myogenic
metabolic
tissue pressure
myogenic mechanism of autoregulation
the vascular smooth muscle contracts in response to stretch and relaxes with a reduction in the stress
metabolic mechanisms of autoregulation
blood flow is linked to the metabolic activity of the tissue
a change in the oxygen supply will produce a change in the amount of a “metabolite” that is vasoactive
tissue pressure mechanism of autoregulation
a change in perfusion will produce a change in the interstitial pressure, which will change the external force on the blood vessels in the tissue
most operable in tightly encapsulated tissue (limited compliance)
hyperemia
imbalance between oxygen supply and demand that leads to a relative increase in blood flow
functional - due to increased metabolism
reactive - due to metabolic debt
endothelial factors
nitric oxide
prostacyclin
endothelin 1
endothelial dependent hyperpolarizing factor (EDHF)
prostacyclin
an arachidonic acid metabolite with actions similar to NO
released from endothelial cells in response to many stimuli including hypoxia, shear stress, acetylcholine, and platelet products such as serotonin
causes relaxation of vascular smooth muscle through cAMP mechanisms
endothelial dependent hyperpolarizing factor (EDHF)
also acts like nitric oxide
hyperpolarizes adjacent vascular smooth muscle cells and causes relaxation
endothelin 1
potent vasoconstrictor
produced by endothelial cells in response to stimuli
under normal circumstance, vasodilator influences predominate
nitric oxide synthesis
interaction of endothelium with platelets
in the absence of vascular injury, the vasodilators regulate platelet interaction and vessel dilation
in the case of injury, vasodilators are downregulated, and this promotes vessel contraction as well as allows platelet aggregation
promoters of vascular growth
vascular endothelial growth factor (VEGF) - tyrosine kianse receptor
fibroblast growth factors (FGFs) - embryonic, fetal, and postnatal development
angiopoietin-1 (ANGPT1) - endothelial cells, required for embryonic vascular development
inhibitors of vascular growth
EC matrix of tumros and breakdown product of collagen XVII to make endostatin
angiostatin from plasminogen - enhanced apoptosis of endothelial cells
angiopoietin-2 (ANGPT2) - antagonist of ANGPT1
epinephrine
potent vasoconstrictor and cardiac stimulant
beta1 - chronotropic for heart
beta2 - dilates muscle vessels
alpha receptors lead to vasoconstriction in the veins and vasodilation in the arterioles due to the beta2 effect
