Smooth Muscle Contraction

• There are 3 types of smooth muscle in the body that contract differently.
• Smooth muscle can be found in the walls of hollow organs involved in gas, liquid, and solid transport like the lungs, bladder, and gut.
• Smooth muscle lacks the striated appearance seen in skeletal and cardiac muscle under a microscope.
• The autonomic nervous system and hormones control smooth muscles.
• Pacemaker cells control the GI tract leading to rhythmic contractions.
• Excitation-contraction coupling in smooth muscle differs from striated muscle.
• Dense bodies and adherens junctions serve as anchor points in smooth muscle cells.
• When smooth muscle contracts, the distance between actin filaments shortens.
• The sarcoplasmic reticulum stores intracellular calcium.
• Gap junctions between smooth muscle cells allow electrical activity to pass.
• Phosphorylation of the myosin light chain enables the myosin head to interact with actin.
• This triggers contraction by starting the crossbridge cycle.
• Myosin light chain kinase (MLCK) and myosin light chain phosphatase (MLCP) are key drivers of contraction and relaxation.
• Calcium is needed to activate MLCK, which binds to calmodulin to drive phosphorylation.
• Smooth muscle contraction or relaxation controls vascular tone.
• Contraction of vascular smooth muscle can be controlled by neurotransmitters and hormones.
• Smooth muscle cells feature slow depolarizations rather than firing action potentials.
• Drugs treating hypertension can be dangerous to the heart.
• Hypertension (high blood pressure) is a risk factor for heart disease and stroke, defined as BP > 140/90 mmHg (systolic/diastolic).
• 30% of adults over 35 in the UK have hypertension.
• Hypertension treatment combines lifestyle changes and medication.
• Blood pressure (BP) can be calculated with the equation: Cardiac output (CO) x Total peripheral resistance (TPR)
• Many hypertension drugs lower blood pressure by reducing TPR, leading to vasodilation.

Classes of Hypertension Drugs

• Alpha-1-adrenoceptor antagonists (e.g., prazosin) block vasoconstriction by noradrenaline.
• Beta-1 adrenoceptor antagonists (beta-blockers) (e.g., propranolol) inhibit SNS effects on the heart, reducing cardiac output.
• Calcium channel blockers (e.g., nifedipine) block voltage-operated calcium channels in smooth muscle.
• Diuretics (e.g., bendroflumethiazide) increase fluid loss, reducing blood volume.
• Drugs that inhibit the Renin-Angiotensin-Aldosterone-System (RAAS) interfere with hormones that regulate blood volume and vasoconstriction.

Renin-Angiotensin-Aldosterone System (RAAS)

• The RAAS is a means of maintaining blood pressure.
• Hormones released into circulating blood carry out its effects, unlike the autonomic nervous system.
• Activation of the RAAS increases blood pressure.
• Drugs that inhibit the RAAS treat hypertension.

Endothelium-Derived Relaxing Factor (EDRF)

• In 1980, scientists discovered endothelial cells release a substance relaxing nearby vascular smooth muscle.
• This substance was named Endothelium Derived Relaxing Factor (EDRF).
• In 1987, EDRF was identified as nitric oxide (NO).
• Nitric oxide (NO) is released by the endothelium in response to stimuli such as bradykinin, histamine, low pH, ATP, and increased blood flow.
• Inhibition of NO release increases blood pressure, and a healthy vascular endothelium is vital for cardiovascular health.

Nitric Oxide

• Nitric oxide relaxes vascular smooth muscle and a number of clinically useful drugs mimic, or enhance its actions.
• Nitrovasodilator drugs such as sodium nitroprusside and glyceryl trinitrate decompose in blood plasma to release NO.
• Nitrovasodilator drugs are used to treat angina, but are too short acting to treat hypertension.
• PDE-5 inhibitors (e.g., sildenafil/Viagra) stop the breakdown of cGMP, prolonging its actions.
• PDE-5 inhibitors are used to treat erectile dysfunction and pulmonary hypertension.