Vascular Pharmacology (Block 3) Flashcards
Arterioles and the sympathetic nervous system
Arterioles are heavily innervated by the sympathetic nervous system (alpha-1-receptors), especially in digestive, renal, cutaneous and skeletal muscule vascular beds.
Elastin provides ?
Elasticity
Collagen provides?
Stiffness
Microcirculation
The smallest arterioles, capillaries, and post-capillary venules
Allow for transfer of gases, H2O, nutrients, and waste products between blood and tissues <- the ultimate function of the cardiovascular system
Control of vascular smooth muscle
Contract when Ca2+ increases but link is looser than in other muscles
Vasoconstrictors and vasodilators can act by:
increasing or decreasing Ca2+ levels and/or changing the sensitivity of the contractile machinery to Ca2+
How is the actin potential generated in smooth muscle?
by L-type Ca2+ channels,rather than voltage-gated Na+ channels.
Vascular endothelium
Provides signals that regulate vascular zone, haemostasis, and thrombosis.
Endothelial cells synthesise a variety of vasoreactive mediators
Vasoreactive mediators synthesised by endothelial cells include:
Prostanoids
Nitric oxide (NO)
C natriuretic and adrenomedulin
ACE (angiotensin-converting enzyme)
Protanoids
PGI2 (prostaglandin I2 or prostacyclin) & PGE2 (vasodilators)
PGG2 & PGH2 are vasoconstrictors, acting via thromboxane receptors
Nitric oxide
NO is a vasodilator acting via guanylate cyclase. It is released in resistance vessels
NO also inhibits platelet aggregation and SMC proliferation
ACE
Produces angiotensin II (AII), a potent vasoconstrictor
C natriuretic peptide & adrenomedulin
Vasodilators
Blood pressure is proportional to
Cardiac output (CO) and peripheral resistance (PR)
Resistance is dependent on
Blood vessel size
Elasticity
Geometry
Blood viscosity
When does peak blood pressure occur?
During systole (left ventricular contraction into the aorta)
When does the lowest blood pressure occur? (When does it trough?)
During diastole (left ventricular relaxation and filling of returning blood)
Vasoconstrictors
Constrict smooth muscle
Act ether directly or indirectly
Main groups of vasoconstrictors
alpha-1-adrenoceptor agonists
sympathomimetic amines (release noradrenaline, or inhibit its reuptake)
peptides, including angiotensin (Ang II) & endothelin (ET-1)
others, including some eicosanoids (e.g. thromboxane A2)
Vasodilators
Relax smooth muscle
Therefore reduce cardiac work
How do vasodilators work?
• Block of Ca2+ entry
- directly, by block of voltage-gated Ca2+ channels
(e.g. nifedipine, verapamil and diltiazem)
- indirectly by hyperpolarisation of cell
(e.g. K+ channel activators minoxidil & cromokalim)
• Affecting enzymes that control Ca2+ sensitivity
- increasing cAMP
(e.g. 2 agonists and PGI2)
- increasing cGMP
(e.g. NO, nitroprusside and natriuretic peptides)
Therapeutic uses of vasodilators
To treat hypertension, angina, and cardiac failure
Renin-angiotensin system
Important role in regulating blood volume, arterial pressure, and cardiac and vascular function.
Renin is released from kidney
Levels increased by a range of factors [1]
Catalyzes first step in formation of angiotensin II [2]
Angiotensin II is a potent vasoconstrictor
Renin
Kidney-derived protease
Renin is secreted in response to what stimuli?
Reduced renal Na+
Reduced renal perfusion pressure
Renal sympathetic nerve activity
Beta-adrenoreceptor agonists and PGI2
