Lecture 11: Regulation of vascular smooth muscle

Question 1

Describe the different electrical signals in vascular smooth muscle

Answer 1

Frequency dependent - includes APs
slow depolarizing waves - may or may not include APs,
tonic depolarisation induced waves - tonic, graded
pharmacomechanical coupling - force generation without depolarisation

Question 2

Describe neural regulation of vascular smooth muscle

Answer 2

sympathetic regulation. ATP and NE released. ATP binds to purinergic receptor P2X. P2X opens, is non selective cation channel, but this causes increase in Ca2+. Also allows Na in, causes depol. This is the fast response. NE acts on alpha1, activates Gq/PLC channel, eventually Ca release from SR. this is the moderately fast release. Finally, with a strong enough stimulation, neuropeptide Y is released and binds to the Y1 receptor, and through a long pathway, also increases calcium. this is the slow response.

Question 3

Describe the 4 different ways of endothelial regulation

Answer 3

1) EDRF
2) endothelin
3) EDHF
4) prostanoids

Question 4

Describe the EDRF pathway

Answer 4

EDRF causes vasodilation. Acetylcholine activates M3 receptor, Gq, follows PLC pathway to increase Ca2+. This activates eNOS, endothelial nitric oxide synthase, to convert L-arginine to NO. NO in the endothelium then crosses to the vascular smooth muscle. It activates guanylyl cyclase, which converts GTP to cGMP. cGMP then activates PKG. PKG phosphorylates and inhibits MLCK., also phosphorylates PLB to allow SERCA to increase. cGMP is converted to GMP by phosphodiesterase 5

Question 5

Describe the endothelin pathway

Answer 5

endothelin binds to ETa or ETb receptor, ETa is in SMC and high pressure vessels, activates Gq and PLC pathway to cause vasoconstriction. ETb is in low pressure vessels, stimulates eNOS to cause vasodilation.

Question 6

Describe the EDHF pathway

Answer 6

Activates the K+ channels, hyperpolarizes the cell and inactivates CaV1.2, therefore causes vasodilation.
One EDHF is EETEs

Question 7

Describe regulation by other tissues (mast cells, kidney, pituitary, and surrounding tissue)

Answer 7

1) mast cells release histamine, histamine binds to H1 receptor, and causes inflammation response. activates eNOS, causes vasodilation
2) kidney produces renin. eventually leads to angiotensin 2, which binds to angiotensin 1 receptors, causes vasoconstriction through Gq, PLC pathway
3) Pituitary/hypothalamus releases ADH, prevents water loss and causes vasoconstriction
4) surrounding tissue releases local metabolites, causes vasodilation