LAUSR

Nature reviews | Nephrology the renin–angiotensin system regulates blood pressure (BP) and mounting evidence indicates that biological sex affects the pathways activated by these hormonal mediators. Now, Jose romero and colleagues report a sex bias on the effects of endoplasmic reticulum aminopeptidase 1 (eraP1) deficiency. “we had previously reported an effect of biological sex on systolic BP responses to angiotensin ii (angii), a potent vasoconstrictor and inducer of aldosterone secretion from the adrenal gland,” explains romero. “we then focused our studies on eraP1, which had been shown to degrade AngII in vitro.” “in female and male mice, eraP1 deficiency increased tissue angii — systolic BP, diastolic BP and salt sensitivity of BP were also increased, indicating that loss of eraP1 leads to volume expansion,” remarks romero. However, despite similar increases in BP, aldosterone levels increased in Erap1+/– males but not in females. Volume expansion would be expected to increase renal plasma flow, but this physiological response was only observed in male Erap1+/– mice; glomerular volume also only increased in Erap1+/– males. therefore, despite an increase in BP, eraP1 deficiency did not induce renovascular changes in female mice. in humans, homozygosity for the ERAP1 rs30187 lossof-function polymorphism was significantly associated with higher BP than no expression of the risk allele or heterozygosity — this effect was only observed in males, not females. “Our results suggest that men homozygous for the rs30187 risk allele might benefit more from therapeutic angii receptor blockade or angiotensinconverting enzyme (aCe) inhibition than women,” notes romero. “Our study provides a rationale for clinical trials that specifically assess the effects of biological sex on BP control through angii blockade, aCe inhibition and mineralocorticoid receptor antagonism,” concludes romero. Monica Wang H Y P E RT E N S I O N