Lecture 7 Physiology of the Vasculature I Flashcards
What are the different types of blood vessels
Large arteries medium-sized arteries arterioles capillaries venules medium-sized veins and large veins
Outline the structure of the vascular wall
The innermost layer surrounds the lumen of the vessel and is called the tunica intima. This consists of a single cell layer of endothelial cells attached to the basement membrane. The next layer is the tunica media this layer contains the vascular smooth muscle as well as elastic tissue. The relative proportion of elastic tissue and vascular smooth muscle varies between different types of vessels. The outermost layer is the tunica adventitia or tunica externa. This consists of a protective layer made up of fibrous connective tissue and extracellular matrix proteins such as collagen
Below is a histological staining of a blood vessel label the endothelium vascular smooth muscle and fibrous connective tissue layers on the diagram
![](https://s3.amazonaws.com/brainscape-prod/system/cm/246/311/063/q_image_thumb.png?1520091803)
See completed labels
![](https://s3.amazonaws.com/brainscape-prod/system/cm/246/311/063/a_image_thumb.png?1520091811)
What are the two main ways that the endothelium and adjacent VSMCs communicate
Gap junctions and via the release of mediators from the endothelium that act on the vascular smooth muscle
What is the role of the glycocalyx
Under normal conditions where the endothelium lining the blood vessels is healthy there is a layer on top known as the glycocalyx. This consists of carbohydrate chains attached to the cell membranes of the endothelial cells. The glycocalyx as an anti-coagulant effect by preventing circulating cells from binding to the endothelial layer
What happens to the glycocalyx in disease and what is the effect of this
Activated/Dysfunctional endothelium in disease will shed the glycocalyx. This exposes cell adhesion molecules (CAMs) that allow immune system cells such as monocytes neutrophils and platelets to bind to the endothelium
Glycocalyx shedding is a phenomenon that only happens in disease T or F
F - Glycocalyx shedding is a normal response tissue injury infection and inflammation
Other than disease what other factors can cause glycocalyx shedding
Glycocalyx shedding can also occur at disturbed blood flow. This is where eddies and turbulent flow causes loss of glycocalyx
Outline the healthy endothelial cell signalling that goes on in the blood vessels
In healthy endothelium neurotransmitters such as acetylcholine histamine 5-HT and bradykinin bind to receptors and increase Ca2+. A rise in intracellular Ca2+ activates endothelial nitric oxide synthase (eNOS) which then converts arginine into NO and citrulline. NO diffuses out of the endothelium and acts on adjacent smooth muscle cells where it causes relaxation
High shear blood flow also increases Ca2+ and activates eNOS T or F
T
Outline what happens in activated endothelium during disease
Activated endothelium have shed their glycocalyx and then IL-1 thrombin and endotoxins activate the receptors of the endothelial cells leading to the production of endothelin 1 (ET-1). Meanwhile there is an increased upregulation of ROS ICAM-1 VCAM1 IL-8 and COX2. All these pathway act to cause vascular disease
Explain the role of Ca2+ and its downstream targets in the contraction of VSMCs
Activation of Ca2+ channels in the plasma membrane of the endothelium leads to an influx of Ca2+ ions. This rise in intracellular Ca2+ activates calmodulin. Calmodulin in the presence of Ca2+ activates MLCK which then phosphorylates inactive myosin allowing it to bind actin. Once phosphorylated and bound to actin myosin can mediate the contraction of the smooth muscle
What intrinsic mechanism in smooth muscle accounts for its relaxation
Myosin light chain phosphatase (MLCP) causes the relaxation of VSMCs by dephosphorylating myosin. This enzyme is constrictively active in the vasculature meaning that it will trigger relaxation as soon as the contractile stimuli has passed
What are the key differences between skeletal muscle and VSMCs
In contrast to skeletal muscle myosin in vascular smooth muscle needs to be phosphorylated in order to bind actin. The other key difference is that myosin light chain phosphatase (MLCP) is constitutively active in VSMCs and hence as Ca2+ levels fall there is a natural relaxation
How else can Ca2+ levels be raised inside vascular smooth muscle cells in order to trigger contraction
Receptors that activate IP3 can also lead to VSMC contraction via acting on IP3R and RyR1 receptors to cause store release of Ca2+
What are the two classes of contractile stimuli in the VSMCs
GPCRs that are GαQ coupled these activate PLC-γ and increase IP3 levels which feeds in to Ca2+. The other class are Ca2+ channels which act to directly increase intracellular Ca2+
Give some examples of contractile stimuli that raise IP3 levels
Endothelin A/B receptors the thromboxane prostanoid receptor (TP-R) the AT-1 (angiotensin II) receptor the histamine receptor as well as the αARs