Human evolution, uric acid, hypertension, atherosclerosis and PS

[Guest guest]

Hi All,

It was interesting for me to find an article (below, PDF is available) that

studied the Paleolithic basis for salt-sensitivity and concluded that there

were mutations in the pathway for uric acid production that occurred during

a late event in human evolution in response to the low-salt nature of the

diets at the time. Then when modern man started using relatively high salt

levels, it led to an epidemic of hypertension and moreover heart disease.

In related matters, Dean might want to consider blood pressure more

important during his randomized control salt trials and also to watch if

possible his uric acid levels. His like mine are generally below normal

range in accordance with low blood pressures.

Looking at the post of crdude this morning, I thought he had maybe suggested

that rhesus monkeys are chimpanzees. The molecular evolution of the

primates apparently shows that chimpanzees share the salt sensitivity with

humans and are closely related and both distant from monkeys.

Watanabe S, Kang DH, Feng L, Nakagawa T, Kanellis J, Lan H, Mazzali M,

RJ.

Uric acid, hominoid evolution, and the pathogenesis of salt-sensitivity.

Hypertension. 2002 Sep;40(3):355-60.

“…... All primate species examined (common chimpanzee, pygmy chimpanzee,

gorilla, orangutan, gibbon, baboon, rhesus monkey, green monkey, owl monkey,

and galago) tested positive for a copy of the distal element. In addition to

humans, only the chimpanzee was found to have a copy of the proximal

CMT1A-REP element………. . . Mild hyperuricemia in rats acutely increases blood

pressure by a renin-dependent mechanism that is most manifest under low-salt

dietary conditions. Chronic hyperuricemia also causes salt sensitivity, in

part by inducing preglomerular vascular disease. The vascular disease is

mediated in part by uric acid-induced smooth muscle cell proliferation with

activation of mitogen-activated protein kinases and stimulation of

cyclooxygenase-2 and platelet-derived growth factor. Although it provided a

survival advantage to early hominoids, hyperuricemia may have a major role

in the current cardiovascular disease epidemic”.

PMID: 12215479 [PubMed - indexed for MEDLINE]

“……..The sodium content of early hunter-gatherers of the Paleolithic Period

was also extremely low and has been estimated to be only 690 mg/d

(equivalent to 30 mEq Na+ or 1.9 g NaCl).12 In contrast, the average sodium

intake in the current American diet averages 4000 mg/d (170 mEq Na+ or

approximately 10 g NaCl). Although individuals with normal kidneys might be

able to excrete the increased sodium content without altering systemic blood

pressure, there is evidence that individuals who develop essential

hypertension have a relative defect in their ability to excrete sodium.13

…….. As discussed above, the sodium intake of the early hunter-gatherers in

the middle to late Pleistocene was in the range of 690 mg (1.9 g NaCl) per

day. The sodium intake of early hominoids during the Miocene epoch (from 24

to 5 million years ago) was likely even lower, because the diets consisted

primarily of fruits (frugivorous) or leaves (foliverous). Eaton and Konner

estimated that the sodium content of a strictly vegetarian Paleolithic diet

may have amounted to only 225 mg sodium (10 mEq Na+ or 0.6 g NaCl).12 Thus,

the climatic shift to more arid conditions in the middle to late Miocene may

have placed selection pressure on the early primates toward a genotype that

would maximally conserve sodium with the maintenance of blood pressure……..

Most authorities16,19,21 have proposed that the mutations in the uricase

gene provided an evolutionary advantage because uric acid may function as an

antioxidant.29…….

mild hyperuricemia was induced in rats by administering the uricase

inhibitor, oxonic acid, and then, to recreate the prehistoric conditions, we

placed the rats on a low-salt (0.125% NaCl) diet.14,15 Normal rats on a

low-salt diet have either no change or a gradual fall in blood pressure; in

contrast, hyperuricemic rats increase their blood pressure (Figure 2).14 The

increase in blood pressure correlated with the uric acid levels and could be

prevented by lowering the uric acid levels with allopurinol (a xanthine

oxidase inhibitor) or with benziodarone (a uricosuric agent). The increase

in blood pressure in hyperuricemic rats was shown to be mediated in part by

stimulation of the renin angiotensin system.14 This hormonal system has a

key role in maintaining blood pressure, glomerular filtration rate, and

sodium balance under low-salt dietary conditions. We also found that

hyperuricemic rats develop vascular disease, particularly of the afferent

arteriole of the renal microvasculature, as well as mild renal interstitial

inflammation and tubular injury.14,15 These renal lesions, as well as the

renin activation, could be prevented by lowering the uric acid with either

allopurinol or benziodarone. The arteriolar lesion resembled the

arteriolosclerosis observed in patients with essential hypertension, but the

lesion occurred independently of blood pressure as a consequence of a direct

stimulation of the vascular smooth muscle cells by uric acid.15…..

In modern society the switch to a high salt diet, coupled with this

mutation, may have an important role in the current epidemic of hypertension

and cardiovascular disease. Other dietary factors (such as dietary changes

in potassium and magnesium) and the development of obesity are also likely

to be contributory factors for the development of hypertension……”.

PS: I also found:

http://www.health.harvard.edu/article.cfm?id=84

Henry Huxley, the 19th-century British scientist, said that science

has many examples of beautiful hypotheses slain by ugly facts. Many " ugly

facts " show that vitamin E supplements have little if any benefit for the

heart.

Cheers, Al.

Alan Pater, Ph.D.; Faculty of Medicine; Memorial University; St. 's, NF

A1B 3V6 Canada; Tel. No.: (709) 777-6488; Fax No.: (709) 777-7010; email:

apater@...