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Estrogen‐Dependent Upregulation of the Renin Angiotensin System and Constitutive NOS Accounts for Ethanol Enhancement of Enalapril‐Evoked Hypotension in Telemetered Female Rats
Author(s) -
ElMas Mahmoud,
AbdelRahman Abdel
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.624.1
Subject(s) - enalapril , endocrinology , medicine , enos , ovariectomized rat , chemistry , renin–angiotensin system , nitric oxide synthase , ethanol , angiotensin converting enzyme , estrogen , bradykinin , enalaprilat , downregulation and upregulation , ace inhibitor , angiotensin ii receptor type 1 , nitric oxide , receptor , blood pressure , biochemistry , gene
We have previously reported that chronic ethanol enhances the hypotensive effect of enalapril in female rats. Here, we investigated whether this effect of ethanol is estrogen‐dependent and whether the renin‐angiotensin system (RAS) and nitric oxide synthase (NOS) constitute molecular targets for the ethanol‐enalapril interaction. Four groups of telemetered rats were employed, 2 ovariectomized (OVX), and 2 estrogen‐replaced OVX rats (OVXE 2 ), and allocated to receive liquid diet containing 5% w/v ethanol or isocaloric diet for 13 weeks. In OVXE2 but not OVX rats, ethanol feeding significantly increased renal angiotensin II level, and protein expressions of angiotensin converting enzyme, AT1 receptors, eNOS, and nNOS. Enalapril (10 mg/kg i.p) caused similar reductions in BP in OVX and OVXE2 rats. The hypotensive effect of enalapril was significantly increased in OVXE2/ethanol, but not in OVX/ethanol rats. The augmented enalapril‐evoked hypotension in OVXE2/ethanol rats was still evident in the presence of 1400W (iNOS inhibitor), but it was virtually abolished by prior inhibition of eNOS (L‐NIO), or nNOS (NPLA), or blockade of bradykinin B 2 receptors (B 2 R, bradyzide). Together, RAS upregulation, along with facilitated B 2 R/eNOS/nNOS signaling, underlie the estrogen‐dependent enhancement of enalapril‐evoked hypotension in ethanol‐fed rats.