Sex-Specific Modulation of Blood Pressure and the Renin-Angiotensin System by ACE (Angiotensin-Converting Enzyme) 2.

Autor:	Ji H; From the Division of Nephrology and Hypertension, Department of Medicine (H.J., A.M.A.d.S., B.B., W.Z., X.W., K.S.), Georgetown University, Washington, DC.; Center for the Study of Sex Differences in Health, Aging and Disease (H.J., A.M.A.d.S., B.B., W.Z., X.W., K.S.), Georgetown University, Washington, DC., de Souza AMA; From the Division of Nephrology and Hypertension, Department of Medicine (H.J., A.M.A.d.S., B.B., W.Z., X.W., K.S.), Georgetown University, Washington, DC.; Center for the Study of Sex Differences in Health, Aging and Disease (H.J., A.M.A.d.S., B.B., W.Z., X.W., K.S.), Georgetown University, Washington, DC., Bajaj B; From the Division of Nephrology and Hypertension, Department of Medicine (H.J., A.M.A.d.S., B.B., W.Z., X.W., K.S.), Georgetown University, Washington, DC.; Center for the Study of Sex Differences in Health, Aging and Disease (H.J., A.M.A.d.S., B.B., W.Z., X.W., K.S.), Georgetown University, Washington, DC., Zheng W; From the Division of Nephrology and Hypertension, Department of Medicine (H.J., A.M.A.d.S., B.B., W.Z., X.W., K.S.), Georgetown University, Washington, DC.; Center for the Study of Sex Differences in Health, Aging and Disease (H.J., A.M.A.d.S., B.B., W.Z., X.W., K.S.), Georgetown University, Washington, DC., Wu X; From the Division of Nephrology and Hypertension, Department of Medicine (H.J., A.M.A.d.S., B.B., W.Z., X.W., K.S.), Georgetown University, Washington, DC.; Center for the Study of Sex Differences in Health, Aging and Disease (H.J., A.M.A.d.S., B.B., W.Z., X.W., K.S.), Georgetown University, Washington, DC., Speth RC; Department of Pharmaceutical Science, School of Pharmacy, Nova South Eastern University, Fort Lauderdale, FL (R.C.S.)., Sandberg K; From the Division of Nephrology and Hypertension, Department of Medicine (H.J., A.M.A.d.S., B.B., W.Z., X.W., K.S.), Georgetown University, Washington, DC.; Center for the Study of Sex Differences in Health, Aging and Disease (H.J., A.M.A.d.S., B.B., W.Z., X.W., K.S.), Georgetown University, Washington, DC.
Jazyk:	angličtina
Zdroj:	Hypertension (Dallas, Tex. : 1979) [Hypertension] 2020 Aug; Vol. 76 (2), pp. 478-487. Date of Electronic Publication: 2020 Jun 22.
DOI:	10.1161/HYPERTENSIONAHA.120.15276
Abstrakt:	We showed ACE (angiotensin-converting enzyme) 2 is higher in the kidney of male compared with female mice. To further investigate this sex difference, we examined the role of ACE2 in Ang-[1-8] (angiotensin [1-8])-induced hypertension and regulation of the renin-angiotensin system in the kidney of WT (wild type) and Ace2 KO (knockout) mice. Mean arterial pressure rose faster in WT male than WT female mice after Ang-[1-8] infusion. This sex difference was attenuated in ACE2 KO mice. Ang-[1-8] infusion reduced glomerular AT1R (angiotensin type 1 receptor) binding in WT female mice by 30%, and deletion of Ace2 abolished this effect. In contrast, Ang-[1-8] infusion increased glomerular AT1R binding in WT male mice by 1.2-fold, and this effect of Ang-[1-8] persisted in Ace2 KO male mice (1.3-fold). ACE2 also had an effect on renal protein expression of the neutral endopeptidase NEP (neprilysin), the enzyme that catabolizes Ang-[1-10] (angiotensin [1-10]), the precursor of Ang-[1-8]. Ang-[1-8] infusion downregulated NEP protein expression by 20% in WT male, whereas there was a slight increase in NEP expression in WT female mice. Deletion of Ace2 resulted in lowered NEP expression after Ang-[1-8] infusion in both sexes. These findings suggest sex-specific ACE2 regulation of the renin-angiotensin system contributes to female protection from Ang-[1-8]-induced hypertension. These findings have ramifications for the current coronavirus disease 2019 (COVID-19) pandemic, especially in hypertension since ACE2 is the SARS-CoV-2 receptor and hypertension is a major risk factor for poor outcomes.
Databáze:	MEDLINE
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