Response to Evolution and Hypertension: Is the Renin System Necessary?
Gavras and Brunner1 make the salient point that the renin– angiotensin–aldosterone system (RAAS) is not completely suppressed by our habitually high sodium intake. From an evolutionary standpoint, this is perhaps to be expected, because the system was presumably adapted for sodium conservation, and elimination of a sodium load is a much different physiological problem. It seems plausible that in the hot, dry environments favoring sodium retention, phenotypic features arising from the genetic variants favored by natural selection might include incomplete suppression of sodium-retaining mechanisms, as appears to be the case for individuals with the A (–6) allele of the angiotensinogen gene.2,3 Conversely, in environments in which there is less selection pressure for sodium retention, alleles of the AGT gene associated with lesser activity of the RAAS could arise and be positively selected, as has been suggested in a recent genomic analysis.4 Thus, as a species we appear to be adapting to the novel environment of northern latitudes by selection for lesser RAAS activity. It will indeed be interesting to see whether renin inhibitors, which may more completely suppress RAAS activity than currently available pharmacological agents, will obviate the race-related differences in RAAS activity and lead to the benefits for cardiovascular and renal outcomes that Gravas and Brunner1 anticipate.
Gavras H, Brunner HR. Evolution and hypertension: is the renin system necessary? Hypertension. 2007; 49: e36.
Nakajima T, Wooding S, Sakagami T, Emi M, Tokunaga K, Tamiya G, Ishigami T, Umemura S, Munkhbat B, Jin F, Guan-jun J, Hayasaka I, Ishida T, Saitou N, Pavelka K, Lalouel J-M, Jorde LB, Inoue I. Natural selection and population Evolution and population history in the human angiotensinogen gene (AGT): 736 complete AGT sequencesin chromosomes from around the world. Am J Hum Genet. 2004; 74: 898–916.