What controls blood flow through vessels?
The contraction of vascular smooth muscle, which causes vasoconstriction.
What triggers vascular smooth muscle contraction?
An increase in intracellular calcium concentration ([Ca2+]i).
List three mechanisms by which agents cause vascular smooth muscle contraction.
1) IP3-mediated Ca2+ release from ER/SR, 2) Ligand-gated Ca2+ entry (e.g., ATP-mediated), 3) Depolarization opening voltage-gated Ca2+ channels.
How does calcium cause smooth muscle contraction?
Ca2+ binds to calmodulin, activating myosin light-chain kinase (MLCK), which phosphorylates myosin, allowing contraction.
How is smooth muscle relaxation achieved?
cAMP inhibits MLCK, and cGMP activates myosin phosphatase (MP), which dephosphorylates myosin, causing relaxation.
List three ways agents can cause vascular smooth muscle relaxation.
1) Inhibit receptors that activate PLC/IP3 pathway, 2) Block voltage-gated Ca2+ channels, 3) Increase intracellular cAMP or cGMP.
What is the mechanism of nifedipine?
It blocks voltage-gated Ca2+ channels, preventing Ca2+ influx and smooth muscle contraction.
What is nifedipine used for?
Treatment of hypertension and angina (vasodilation).
How do α1-adrenoceptors affect vascular smooth muscle?
They activate PLC and increase IP3, leading to smooth muscle contraction (vasoconstriction).
What drugs block α1-adrenoceptors and what are they used for?
Prazosin, terazosin, and doxazosin; they cause vasodilation and are used to treat hypertension.
What effect do potassium channel activators have on vascular smooth muscle?
They open K+ channels, causing hyperpolarization, which closes voltage-gated Ca2+ channels and leads to relaxation.
Give an example of a potassium channel activator and its mechanism.
Cromakalim; opens K+ channels, hyperpolarizes the membrane, and prevents Ca2+ influx, causing vasodilation.
How do endothelial cells regulate vascular tone?
They release mediators that cause either smooth muscle contraction or relaxation.
Which two mediators cause smooth muscle relaxation?
Nitric oxide (NO) and prostaglandin I2 (PGI2).
What is the mechanism of nitric oxide (NO)?
NO activates guanylate cyclase in smooth muscle, increasing cGMP and activating myosin phosphatase, leading to relaxation.
What is the mechanism of prostaglandin I2 (PGI2)?
PGI2 binds to IP receptors, activates adenylate cyclase, increases cAMP, and inhibits MLCK to cause relaxation.
How can drugs enhance endothelial relaxation?
By increasing intracellular cAMP or cGMP concentrations.
How does angiotensin II cause smooth muscle contraction?
Angiotensin-converting enzyme (ACE) converts angiotensin I to angiotensin II, which binds AT1 receptors and activates PLC → IP3 → Ca2+ release → contraction.
What type of receptor is the AT1 receptor?
A GPCR (G-protein coupled receptor).
What is the mechanism of captopril?
It binds to the active site of ACE, preventing angiotensin I from being converted to angiotensin II.
What are ACE inhibitors used for?
Treatment of hypertension, cardiac failure, and other cardiovascular diseases.
Give an example of an ACE inhibitor.
Captopril.
What drug blocks the AT1 receptor?
Losartan, an AT1 receptor antagonist.
What is the mechanism of losartan?
It blocks angiotensin II binding to AT1 receptors, preventing IP3 production and promoting smooth muscle relaxation.
