This is essential to ensure adequate blood flow reaches tissues to supply their metabolic demand, an important part of homeostasis. There are multiple control mechanisms which can be grouped into local (intrinsic) or systemic (extrinsic).
- Circulatory control of the heart and brain are mainly intrinsic to maintain flow independant of systemic circulation
- Circulation of the skin and gut is largely extrinsically controlled
Increasing or decreasing the tone of smooth muscle within arterioles varies the perfusion pressure across a capillary bed. Vascular smooth muscle is primarily innervated by sympathetic fibres that maintain a baseline level of tone.
Increasing or decreasing the tone here varies intravascular volume as veins contain >60% of blood volume. This has no effect on vascular resistance.
Local mechanisms controlling blood flow
This is the most important as it determines the balance of oxygen supply and demand for tissues. Exposure of tissues to hypoxia or injury causes release of factors that cause vasodilatation independant of systemic control. This varies in spectrum from localised erythema to reperfusion syndrome.
- CO2 and H+ ions: Cause arteriolar vasodilatation. Lactic and pyruvic acid lower pH and have a similar effect.
- Serotonin: Released from platelets at site of mechanical injury, causes vasoconstriction.
- Adenosine, ATP, ADP and AMP: Strong vasodilatory effects. Adenosine dilates hepatic arteries in response to decreased portal blood flow.
Myogenic mechanism: Vascular smooth muscle contracts or relaxes depending on transmural pressure. This means when perfusion pressure varies the flow can remain constant.
Endothelial mechanism: Increases in flow velocity are associated with vasodilalation, probably due to endothelium derived nitric oxide.
Prostacyclin and Thromboxane A2: Arachidonic acid derivatives dependent on cyclo-oxygenase. Prostacyclin is a vasodilator that inhibits platelet aggregation by increasing cyclic AMP preventing vesicular release of thromboxane A2 and von Willebrand factor. Thromboxane A2 is a potent vasoconstrictor which promotes platelet aggregation. These two substances are in balance in health, regular aspirin causes prostacyclin effects to predominate.
Nitric oxide (NO): Potent vasodilator. Synthesised from arginine by NO-synthase and inactivated by haemoglobin. The release from the endothelium can be trigged by substances such as bradykinin and acetylcholine.
Systemic control can be humoral or neurological
Systemic humoral control of blood flow
The most powerful agents responsible for humoral control. Adrenaline is released from the adrenal medulla, with primary effects of the heart. Noradrenaline is released from the adrenal medulla and sympathetic post-ganglionic nerve endings and is a powerful vasoconstrictor.
Otherwise known as anti-diuretic hormone (ADH), this is released from the posterior pituitary in response to increased osmolarity sensed by the osmoreceptors in the hypothalamus. It’s primary action is on the kidney collecting ducts to cause retention of free water, but at supranormal doses it causes systemic vasoconstriction and increased blood pressure.
V1 receptors: Vasoconstriction
V2 receptors: Renal effects
V3 receptors: Modulates secretion of ACTH
NB. Vasopressin is a non-selective V receptor agonist, Terlipressin is a selective V2 agonist.
Formed from angiotensin I in the lungs by angiotensin converting enzyme (ACE). The central effects are to cause the sensation of thirst and release of aldosterone from the adrenal cortex. It is also a powerful peripheral vasoconstrictor.
Atrial Natriuretic Peptide (ANP)
Released from the atria in response to atrial stretch. It causes natriuresis and subsequent loss of free water, lowering blood pressure. It inhibits vasopressin secretion and there is increasing evidence it causes shedding of the endothelial glycocalyx.
Produced in the central nervous system, gastric mucosa and mast cells. Potent vasodilator, it’s release can be inhibited by H1, H2 and H3 receptor antagonism.
Kinins e.g. Bradykinin
Produced from exocrine glands e.g. pancreas, salivary and sweat glands. Vasodilators. ACE is a kinase, which can explain some side effects of ACE-inhibitors e.g. angioedema, cough.
Systemic neurological control of blood flow
All blood vessels except capillaries and venules have smooth muscles in their walls which are supplied by sympathetic motor fibres. These fibres have a normal firing rate or resting tone than can be increased or decreased. Vascular smooth muscle is supplied by noradrenergic sympathetic fibres which increased activity causes vasoconstriction, whereas skeletal muscle is supplied by cholinergic sympathetic fibres in which increased activity causes vasodilatation.
Vasomotor control centres in the CNS
These are located in areas of the reticular formation in the medulla and pons.
Pressor region: Maintains a tonic output to keep a background level of vasomotor tone. It is capable of increasing the heart rate, vascular tone and myocardial contractility.
Depressor region: Inhibits the pressor region.
Efferent – Project directly to preganglionic neurones in the intermediolateral (IML) grey columns of the spinal cord. Preganglionic fibres pass from the IML to the paravertebral sympathetic chain. Post-ganglionic fibres carry sympathetic outflow to effector sites.
Afferent – Baroreceptors in carotid sinus and chemoreceptors in carotid body feed afferent impulse to CNS via the nerve of Herine, a branch of the glossopharyngeal nerve (cranial nerve IX). Aortic baroreceptors relay impulses via the vagus nerve (X). These synapse in the medulla at the nucleus tractus soliatrius (NTS).
Peripheral: Carotid and Aortic bodies
Respond primarily to a reduction in oxygen tension, also senstivie to increase pCO2 and changes in pH. Main effects are on the respiratory centre, though have some minor effects on the pressor region.
Central: Vasomotor centres respond directly to pCO2 and pH.
This central control predominates over peripheral effects. The central receptors are not sensitive to hypoxia.