Dear Sir, pressure of the hemodynamic system is maintained by the carotid body with its baroreceptors and chemoreceptors - Thanks

The purpose of autoregulation is to maintain blood flow to that organ inspite of blood pressure fluctuations by creating pressure gradient in some arterial beds. This does not significantly alter the overall blood pressure. 

4 major mechanisms determine the presence of vascular tone and the ability to autoregulation: neurogenic (autonomic and central nervous system), myogenic (vessels myogenic tone capable to generate impulses spontaneously and independently), humoral (vasoactive substances of local and systemic action) and baroreceptors, as it was mentioned above. Additionally many other factors triger vascular resistance: blood viscosity (temperature, haematocrit, protein content, flow velocity, erythrocytes deformability ), extravascular compression, the state of the collagen-elastin skeleton and others.All the above mentioned - the basis of physiological vessels autoregulation. The disease presence can potentially "change / brakes"  some of the autoregulation mechanisms.

As Yohannes has pointed out above, autoregulation tends to occur on a localized (organ- or tissue-wide) basis. An example, in postural changes, say from going from supine to standing, resistance arteries in the head and neck would experience a sudden drop in pressure; autoregulation would cause them to dilate. In contrast, arteries in the lower leg and feet would experience an increase in pressure, so they would constrict as part of autoregulation. Overall, the net effect of autoregulation in various vascular beds on total peripheral resistance would be roughly balanced.

The other point implied in the question is the 'vicious circle'-type one advanced by Arthur Guyton years ago; that low pressure-induced vasodilation would lead to decreased peripheral resistance, a further fall in pressure, thus more vasodilation and so on until arteries were fully dilated and peripheral resistance was zero. Most studies show there is a pressure-range over which autoregulation occurs. For example, in the cerebral circulation, it's roughly 60 -160 mmHg. At pressures below 60, cerebral arteries don't dilate further; above 160, the arteries won't constrict further. Outside this range, flow in the vessels depends upon systemic mean arterial pressure.      

As pointed out above, the autoregulation mechanisms are governing vascular beds in the most critical for circulation organs: brain, heart, and kidneys. So, when BP drops, the body gives a priority to these organs and other vascular beds are being constricted (hence pallor, peripheral chills and so on) to maintain the systemic BP gradient at the sufficient level. If these autonomic mechanisms are impaired, you may faint or you may faint in extreme situations too (dehydration). It is all about a sophisticated pump and pipe-system where the pipes adapt themselves according to priorities and needs from the whole body perspective. The net effect as pointed out by Timothy is usually balanced but not always ... Check the Orthostatic Hypotension paper on my profile how the baroreceptor reflex works for details but I suppose you know it very well already.

Thank you for all your comprehensive answers. 

I was aware that autoregulation is unlikely to affect total vascular resistance because it is a local tissue/organ response. I just wondered about, at the single artery or local level, what is the signal for the vessel to pressurize again. As Tim said, there are pressure boundaries to which autoregulation will work. Would the dilator autoregulation at lower pressures be simply counteracted by myogenic constriction as that dilator signal switches off at lower pressures, and perhaps constrictor autoregulation by myoendothelial feedback (a question for you, Tim). Or is the picture wider than that, with baroreceptors and nerve input etc?

As illustrated in the figure attached (courtesy Pires et al., 2013), autoregulation (cerebral autoregulation) operated within MAP of 50-150 mmHg. Ideally, the arteries are supposed to dilate or constrict according to perfusion pressure in order to regulate blood flow, and not necessarily generate pressure - resistant arteries (peripheral arterial resistance) and the heart (cardiac output) primarily generate blood pressure and thus perfusion pressure.

When perfusion pressure drops, the vessels dilate, and when the perfusion pressure rises, they constrict to protects smaller arterioles and capillaries from physical damage due to overflow. So, once dilated the arteries remain dilated as far as the perfusion pressure is not restored.  As the perfusion pressure starts to increase the arteries respond by constricting. Below the lower limit of autoregulation, blood flow decreases since the vasodilatation reaches the maximum capacity and the vessels collapse. Equally, as the blood pressure exceeds the upper limit, the arteries are forcefully dilated by the pressure, a condition called ‘breakthrough of autoregulation’, and fail to control the cerebral blood flow. In either case, the person must have already been in emergency and needs clinical assistance, like in cases of shock or hypertensive emergency.

The mediators of autoregulation can be vascular factors (myoendothelial factors), neural (sympathestic) or local metabolic products (H+ or CO2). It is important to note that sympathetic nerves induce constriction in major arteries, but predominantly dilate intra-organ arteries such as the cerebral arteries. That means, when there is blood pressure drops, a reflex activation of sympathetic outflow tries to restore blood pressure, while simultaneously dilating brain arteries and maintain flow, for example. 

 Of particular note is the contribution of metabolic factors such as hpoxia or hypercapnia autoregulation, not to mention neurovascular coupling. For example, hypoxia causes cerebral vasodilation through a number of mechanisms. Decrease in ATP levels due to hypoxia can induce smooth muscle membrane depolarization by activating ATP-dependent K+ channels. Hypoxia can also increase cerebral blood flow by inducing release of vasodilator mediators. Acute hypoxia promotes upregulation of eNOS thus inducing local release of NO. Further, hypoxia induces release of adenosine from endothelial cells.

David asked:

 at the single artery or local level, what is the signal for the vessel to pressurize again.

The answer is...we don't know. If we're talking myogenic (pressure-induced) responses, it's commonly assumed the amount of constriction is regulated by the degree of arterial wall tension (Pressure x radius). But as to what the tension-sensor mechanism is, that is a debate. Lot of interest in TRP channels, especially TRPM4 and maybe TRPCs. Some recent evidence mechanical trans-activation of Ang-II receptors may be involved.

Metabolic autoregulation, there are any number of candidate substances mentioned above, NO, adenosine, pH, etc. The precise role of the endothelium and myo-endothelial coupling is also unclear, our experiments in isolated muscle arteries suggest no role for the endothelium in autoregulation but there is evidence in other vascular beds (esp. coronary and cerebral) that it is involved. It's highly likely there are differences in auto-regulatory mechanism between vascular beds. In vivo might well be a different story, of course, with flow-effects and conducted responses relying on the endothelium. A bit unclear but I hope that helped!  

Dear David,

This is a nice question but difficult to answer!

I agree with Timothy and Yohannes that autoregulation tends to occur on a localized (organ- or tissue-wide) basis. However, much remains still unknown about the regulation of these processes.

In the “classical model” resistance, perfusion pressure and blood flow are commonly defined by the law of Darcy as the quotient between the driving blood pressure and flow (Q=PP/R). This model has limitations, because it assumes that flow or velocity only reaches zero when the driving pressure is zero, which is unlikely. 

The perfusion pressure is defined as the difference between the "effective upstream pressure" (EUP) and the "effective downstream pressure" (EDP). In most cases we use the mean arterial pressure as EUP and the organ-specific venous pressure as EDP.  Studies of organ-perfusion have shown, that the EDP is more determined by a critical closing pressure located at arteriolar level. The concept of “critical closing pressure (CCP)” was considered by Burton and addressed for the cerebral circulation by Greenfield and Tindall and later by Dewey and Early, These studies verified the theory of Permutt and Riley showing that two forces, the extramural pressure (ICP in the case of the brain) and arteriolar wall tension, cause the CCP. Arteriolar wall tension arises from a combination of the stretched elastic components of the vessel wall and active contraction of vascular smooth muscle. Thus, the driving pressure for the flow through arterioles is, under many conditions, not the difference between arterial (inflow) pressure and venous (outflow) pressure, but rather the difference between arterial pressure and CCP.

It has been proven that in vivo pressure/flow relationships are straight lines for many vascular beds and even for the cerebral vessels. The intercept of the pressure/flow plot (zero flow pressure, the pressure when flow ceases), estimated by linear regression, represents vasomotor tone while its slope represents the value of vascular bed resistance. Hence the diameter of the resistance vessel is the relationship between vasomotor tone and vessel diameter.

The brain has no oxygen stores. Furthermore, the space in the skull is limited and volumes of brain tissue, blood, and liquor should have to be constant. Thus, there is a need  of a constant supply / blood flow. It is wonderful that we can sleep, work and sport and our cerebral blood flow (CBF) is still about 50 ml/100g/min. Even a handstand made us not really sick.

In a former investigation, Weyland et al. could support the “alternative model”. Their results confirmed the hypothesis of two Starling resistors in a series connection, one (proximal) at the precapillary level of cerebral resistance vessels (CCPart) and a second (distal) at the level of collapsible cerebral veins (CCPven). Thus, the effective downstream pressure of the cerebral circulation may be determined by either CCP_art, CCP_ven (i.e. ICP), or jugular venous pressure, depending on which one is highest. Thus, the “classical model” must also be considered with limitations.

The changes in vasomotor tone and diameter of the resistances vessel provide a rather constant effective perfusion pressure and thus sufficient blood flow. In cases of a decrease of arterial blood pressure vascular bed stabilize their blood flow by vasodilatation and a decrease in vasomotor tone. Any further decrease of perfusion pressure will lead to an reduced blood flow. 

Greetings from Rotterdam

Frank

PS: here some stuff for further reading :

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Kazmaier S, Hanekop GG, Grossmann M, Dörge H, Götze K, Schöndube F et al. Instantaneous diastolic pressure-flow relationship in arterial coronary bypass grafts. Eur J Anaesthesiol 2006; 23: 373–379.