Smooth Muscle Contraction

• There are 3 types of smooth muscle in the body which contract differently
• Smooth muscle is located in the walls of hollow organs, aiding in the transport of gases, liquids, and solids in areas like the lungs, bladder, and gut
• Smooth muscle lacks the striated appearance seen in skeletal and cardiac muscle under a microscope
• Smooth muscle is controlled by the autonomic nervous system and hormones; in the GI tract, pacemaker cells lead to rhythmic contractions
• Excitation-contraction coupling in smooth muscle differs from that in striated muscle

Organs Containing Smooth Muscle and Their Roles

• Blood vessels (excluding capillaries): Controls blood vessel diameter, impacting vascular resistance, blood flow, and blood pressure
• Gastro-intestinal tract: Controls the mixing and propulsion of GI contents
• Bladder, ureters, urethra: Manages urine storage and urination (micturition)
• Uterus (myometrium): Controls labour
• Respiratory system: Regulates airway diameter, affecting gas flow to/from the lungs
• Vas deferens and penis: Controls ejaculation and erection
• Fallopian tubes: Controls movement of the egg from the ovaries to the uterus
• Iris and ciliary body of eye: Controls pupil diameter and the focal length of the lens

Smooth Muscle Cell Structure

• Dense bodies and adherens junctions: Anchor points
• Black lines: intermediate filaments
• Smooth muscle cell contracts by shortening the distance between actin filaments
• Sarcoplasmic reticulum stores intracellular calcium
• Gap junctions facilitate electrical activity between smooth muscle cells

Regulation of Smooth Muscle Contraction

• Phosphorylation of the myosin light chain enables the myosin head to interact with actin, triggering contraction
• The crossbridge cycle proceeds as in skeletal muscle
• MLCK (myosin light chain kinase) and MLCP (myosin light chain phosphatase) drive contraction/relaxation

Myosin Light Chain Kinase (MLCK) Activation

• Calcium is needed to activate MLCK; it binds to calmodulin, which activates MLCK, driving phosphorylation
• Inhibition of MLCP is called calcium sensitization and promotes contraction
• Activation of MLCP is called calcium desensitization and promotes relaxation
• Contraction or relaxation of vascular smooth muscle (VSM) sets "vascular tone"

Vascular Smooth Muscle

• Vascular smooth muscle is controlled by neurotransmitters and hormones
• Endothelial cells release nitric oxide (NO), which relaxes VSM

Vascular Smooth Muscle Contraction

• Sympathetic nerve fibres release noradrenaline, contracting VSM upon activation of α₁ adrenoceptors
• Substances like angiotensin-2 and adrenaline in the blood also contract VSM
• Smooth muscle cells have slow depolarizations and do not fire action potentials
• Drugs used to treat hypertension can be dangerous as they affect the heart

Hypertension

• Hypertension (high blood pressure) is a major risk factor for coronary heart disease and stroke
• Blood pressure (BP) of greater than 140/90 mmHg (systolic/diastolic) is defined as hypertension
• Around 30% of people over 35 in the UK have hypertension, many undiagnosed
• Treatment combines lifestyle changes (diet, exercise, stress reduction) and drug treatment
• BP = CO (cardiac output) x TPR (total peripheral resistance)
• Many drugs reduce BP by causing vasodilation by relaxing vascular smooth muscle

Classes of Drugs for Hypertension

• α₁-adrenoceptor antagonists (e.g., prazosin): Inhibit vasoconstriction by noradrenaline
• β₁-adrenoceptor antagonists (beta-blockers) (e.g., propranolol): Inhibit the effects of the SNS on the heart, decreasing cardiac output
• Ca2+ channel blockers (e.g., nifedipine): Block voltage-operated calcium channels in vascular smooth muscle
• Diuretics (e.g., bendroflumethiazide): Increase fluid loss through the kidneys, reducing blood volume
• Drugs that inhibit the Renin-Angiotensin-Aldosterone-System (RAAS) are used to treat hypertension

The Renin-Angiotensin-Aldosterone System (RAAS)

• RAAS plays a key role in maintaining blood pressure
• RAAS effects are mediated by hormones released into the circulating blood, unlike the autonomic nervous system
• Activation of RAAS leads to increased blood pressure
• Drugs inhibiting RAAS are important in hypertension treatment

RAAS summary

• Renin is released from the juxtaglomerular cells of the kidney
• ACE is found on the surface of vascular endothelial cells, especially in the lungs
• Aldosterone is released from the adrenal cortex
• Angiotensinogen, angiotensin 1, angiotensin 2, and aldosterone circulate in the blood
• ADH is Anti-Diuretic Hormone

Drugs that Act to Inhibit the RAAS

• ACE inhibitors such as captopril and enalapril can produce a dry cough
• AT1 receptor antagonists, also called Angiotensin Receptor Blockers (ARBs) such as losartan don't cause this side effect

Endothelium Derived Relaxing Factor

• Discovered in 1980 by Furchgott and Zawadzki, showing endothelial cells release a substance that relaxes smooth muscle, causing vasodilation
• EDRF was termed Endothelium Derived Relaxing Factor and identified as nitric oxide (NO) in 1987
• NO is released by the endothelium in response to stimuli, including bradykinin, histamine, low pH, ATP, and increased blood flow
• Inhibition of NO release increases blood pressure; a healthy endothelium is important for cardiovascular health

How NO Relaxes Vascular Smooth Muscle

• Nitrovasodilator drugs (organic nitrates) like sodium nitroprusside and glyceryl trinitrate spontaneously decompose to release NO
• Organic nitrates are used to treat angina by improving blood flow through coronary arteries, but are too short-acting for hypertension
• PDE-5 inhibitors (e.g., sildenafil/Viagra) stop the breakdown of cGMP, prolonging its actions
• Inhibitors are used to treat erectile dysfunction and pulmonary hypertension