David Miller, University of Glasgow and the History & Archives Committee, The Physiological Society

https://doi.org/10.36866/pn.111.29

It is a fascinating fact that the blood pressure, the mean arterial pressure, of mice and men (or women) is much the same. An obvious corollary is that it can thus have little to do with the absolute scale of total peripheral resistance or gravitational effects on the cardiovascular system, given how different we are from mice in both respects. It is the shared requirements of the mammalian ultrafiltration kidney that are predominant in setting the mean arterial pressure … ‘of mice and men’.

A simple thought is rarely noted by the textbooks: why does blood pressure – mean arterial pressure (MAP) – stand at the absolute level that it does? Considerable physiological ‘effort’ is expended by the body in sustaining the regulation of MAP, but why specifically at around 100 mmHg in most mammals, large or small?

Over the years that I was charged with lecturing on the cardiovascular system (CVS) to Glasgow’s medics, dentists and science students, the core concept of blood pressure and its regulation obviously figured large. In any basic course, we devote considerable time to explaining the physiology whereby arterial blood pressure is monitored and, through the interplay of various autonomic, hormonal and ‘local’ mechanisms, regulated. The particulars associated with posture and movement in humans merit attention: the potential for lower limb ‘pooling’ of blood when standing, the consequences of starting – and then sustaining – vigorous physical activity, be it running or static load-lifting. The matter has clear clinical relevance: the consequences of failures in regulation are all too obvious.

Directly asking students – or even colleagues – ‘why is MAP about 100 mmHg?’ commonly generates a vague response along the lines of ‘overcoming the resistance of the vascular tree’ and various aspects of ‘overcoming the effects of gravity’. But MAP is very much the same in cats or horses, as well as in mice or men. Indeed, with some notable and informative exceptions mentioned later, the great majority of mammals have broadly similar MAPs (see Fig. 1 and e.g. Dawson, 2014, Poulsen et al., 2017) with an average around 100 mmHg. The graph shows MAP values for over 40 mammalian species (not individually specified in the source paper) plotted against the body masses on a log scale. Although there is clear variation amongst species of similar body mass, there is no strong correlation with body mass per se, even across four orders of magnitude.
(Note that I am not dealing here with the often considerable, entirely normal MAP variability within species understood to be diurnal, circadian, ambient-temperature or seasonally dependent features, or the effects of hibernation, estivation, etc.) Thus, whatever has determined the absolute value of MAP through evolutionary time, given the huge range of mammalian body sizes and shapes with broadly similar MAPs, it can have had little to do with the absolute peripheral resistance, nor indeed with gravity.

In brief, the physiological system that ‘requires’ the absolute value of MAP we observe is the mammalian ultrafiltration kidney (the inverted commas round ‘requires’ – and elsewhere – are to excuse my short-circuiting millions of years of mammalian evolution in this account. I’ve also neglected birds and other vertebrate classes here. And I am all too aware that asking teleological ‘why?’ questions will offer potential pitfalls). For normal function, the kidney’s glomerular capillary blood pressure (GCP) must be about 60 mmHg, not much higher, or lower. That pressure is in turn defined, for a given species, by largely invariant aspects of blood chemistry, plasma oncotic pressure, capsular hydrostatic pressure and the like that collectively determine how ultrafiltration can proceed. Beyond that, there is an adaptive requirement for mammals to be able to sustain this absolute pressure in the capillaries of Bowman’s capsule despite the range of normal physiological ‘challenges’ to MAP posed by the rest of the system. These challenges include major flow redistributions during exercise, at rest, during digestion-absorption, etc. As junior-level lectures routinely expound, GCP is sustained in the face of these challenges via the autoregulation of glomerular arteriolar tone, neuro- and hormonal regulation and other processes both local to, and remote from, the kidneys. Giving scope for this adaptive requirement is what determines that blood pressure at the proximal end of the glomerular afferent arteriole must be appreciably higher than GCP. Furthermore, there is unavoidably some pressure drop along the renal arterial tree that leads to the afferent arterioles proper. It is these factors defining a rather precise absolute pressure that can explain the ‘set point’ for MAP and the consequent tightness of its homeostatic regulation. In hypothetical terms, the mere perfusion of all other organ systems could readily be achieved at much lower arterial pressures, provided the resistance of those organs and tissues were lower. The pulmonary circulation is an obvious example, albeit one with its own qualifications defining pulmonary flow and blood pressure. The length and sheer quantity of ‘pipes’ per se is clearly not the ‘challenge’ that sets MAP, despite how enticing the idea seems to many: consider once again the mouse-man comparison.

The key point in understanding MAP regulation is that, in general, it is the various regulatory controls that keep total peripheral resistance (TPR) high– much higher than the mere ‘plumbing’ necessitates. The consequence is that, for most organs and tissues most of the time, a considerable pre-capillary drop in pressure is necessarily assured by the resistance of the local arteriolar system. Thus, we could reasonably ask a new question: why is so much force wastefully dissipated across the resistance arterioles most of the time? The advantageous result of high TPR is that a high MAP can be sustained in the face of highly variable, function-dependent flows through the various organs and tissues that are ‘plumbed’ in parallel from the major arteries. It is also an obvious evolutionarily advantage for all mammals to keep their blood volume as low as possible, so a system capable of the ‘demand-dependent’ flow-redistribution of a minimised total blood volume, in tandem with a variable cardiac output, is the evolutionary corollary. The result is that, apart from the situation in the glomerulus of Bowman’s capsule, capillary perfusion pressures are very much lower than MAP (typically at 10-20 mmHg). The consequence of raised capillary perfusion pressures in all these other tissues is oedema – excessive ultrafiltration. Thus, the dissipation of pressure, whilst wasteful on the face of it, ensures that the CVS meets all of these considerations. Overall, the dissipation of pressure in the arterioles of most tissues most of the time has proved evolutionarily advantageous, even if not energy-efficient when seen in isolation.

But ‘what about gravity?’ Isn’t the high MAP ‘needed’ to perfuse the brain? Doesn’t gravity pose a problem, at least for large mammals such as adult humans, when standing? We can put this another way round: if the evolution of an ultrafiltration kidney has delivered an average MAP of about 100 mmHg for most mammals, how far above their hearts could their brains be and yet still be blood-perfused? Decapitation scenes in horror movies are not useful to learning ‘how high’ blood can be pumped. In round figures, 100 mmHg equate to about 13% of one standard atmosphere pressure (760 mmHg). As hobby divers know, 1 Atm is the equivalent of about 10 m depth of water, so 13% means a ‘pressure head’ equivalent to about 1.3 m of water pumped against gravity (and barely less for blood: density 1.06 g/cm3). Thus, even for the tallest humans, the top of the head can be perfused against gravity, provided only that the resistance of the arterial pathway to the head is low enough to minimise that pressure drop and still leave sufficient arteriolar pressure to perfuse the brain thereafter. Clearly, even the tallest mouse or cat has no such gravitational problems, nevertheless their MAP is still much the same as ours. The exceptions that prove the rule here are elephants and especially the giraffe (see Fig.1). The head of a large adult giraffe can rise over two metres above its heart. On my crude calculation, one can anticipate that adult giraffe MAP (at heart level) would need to be nearer 30% of 1 Atm – about 230 mmHg. The measured values are indeed close to that. (There is a fascinating literature exploring, for example, the extent to which a ‘siphon’ effect might be significant in the ‘above the heart’ plumbing of larger mammals, such as humans and the giraffe. Readers are directed there to learn more on the topic, e.g. Hill & Barnard, 1897, Gisolf et al., 2004, Mitchell et al., 2006, White & Seymour, 2013). We can conclude that an evolutionary consequence of MAP averaging around 100 mmHg for most mammals is that it has ‘allowed’ their heads to be up to about a metre or so above their hearts without extensive ‘anti-gravity’ adaptations. However, comparative physiological study of the adaptations seen in the below-the-heart plumbing of larger (taller) mammals also provides useful generic insight into the CVS. (Consider how the low-compliance ‘pressure stocking’ fascia of giraffe limbs ‘combats’ blood pooling near their feet, for example, or that they have very low interstitial colloid osmotic pressure, or how their rete mirabili regulates their brain blood pressures and flows, especially when they lower their heads well below their hearts: see, e.g. Hargens et al., 1987). As perhaps the most extreme ‘gravity-relevant’ insight, recent work on people in Earth orbit (and thus weightless) shows that, despite the significant circulatory changes that do occur, MAP is only marginally affected (typically, but not always, reduced by c10 mmHg).

This topic is one where teleological ‘explanations’ are rife. It is seductive to assert that the body ‘needs’ this or that property or function ‘in order to’ achieve whatever physiological phenomenon is of current interest. Whilst this is often an ‘in-the-trade’ shorthand, we should recognise that non-specialists can too easily be left with an entirely misleading perspective on physiological mechanisms. This essay has in one sense risked a ‘why’ approach, but I trust the evolutionary context for this specific aspect of systems physiology is comprehensible. If my case is compelling, it reinforces the value of comparative physiology and thereby fully recognising ourselves as the evolved animals we are in order to understand our own physiology better. The evolutionary pressures (no pun intended) and opportunities that have delivered the MAP of extant mammals are well worth studying. I hope I have convinced you that neither ‘overcoming peripheral resistance’ nor ‘gravity’ are factors in the front line for any valid account for the magnitude of the mean arterial pressure of most mammals.

Acknowledgements

I am grateful for stimulating comments on an early draft by Charles Michel (Imperial College London), Roger Seymour (University of Adelaide), Otto Hutter and Richard Burton (University of Glasgow).

References

Dawson, TH (2014). Allometric Relations and Scaling Laws for the Cardiovascular System of Mammals Systems 2, 168-185

Gisolf, J, van Lieshout, JJ, van Heusden, K, Pott, F, Stok, WJ & Karemaker, JM (2004). Human cerebral venous outflow pathway depends on posture and central venous pressure J Physiol. 560, 317–327

Hargens, AR, Millard, RW, Pettersson, K & Johansen, K (1987). Gravitational heamodynamics and oedema prevention in the giraffe. Nature 329, 59-60

Hill, L. and Bernard, H. (1897). The influence of the force of gravity on the circulation. Part II. J Physiol. 21, 328-352

Mitchell, G, Maloney, SK, Mitchell, D & Keegan, DJ (2006). The origin of mean arterial and jugular venous blood pressures in giraffes. J. Exp. Biol. 209:2515–2524.

Poulsen, CB, Wang, T, Assersen, K, Iversen, N. K & Damkjær, M. (2017). Does mean arterial blood pressure scale with body mass in mammals? Effects of measurement of blood pressure Acta Physiologica, 222 (4) doi.org/10.1111/apha.13010

White, CR & Seymour, RS (2013).
 The Role of Gravity in the Evolution of Mammalian Blood Pressure. Evolution 68, 901–908