Role of Myocardial Contractility and Autonomic Control in the Hypotensive Response to a Limited Access Ethanol Paradigm in SHRs

Journal of Cardiovascular Pharmacology

Abdel‐Rahman²

2011

Our previous studies showed that chronic ethanol feeding attenuates centrally (clonidine)-and potentiates peripherally (hydralazine)-evoked hypotension in female rats. In this study, we investigated whether chronic ethanol (8 weeks, 5% w/v) alters hemodynamic responses elicited by angiotensin converting enzyme (ACE) inhibition (enalapril) in telemetered female rats. Given the intimate interaction between ACE and bradykinin, studies were extended to investigate the role of bradykinin receptor (B 2 R) in ethanol-enalapril interaction. Compared with pair-fed controls, ethanol-fed female rats exhibited: (i) higher renal expressions of ACE and B 2 R proteins and angiotensin II levels, and (ii) lower blood pressure (BP). Pharmacological inhibition of ACE and B 2 R support functional role for the higher levels of these two proteins in ethanol-fed rats because enalapril (10 mg/kg i.p) caused significantly greater hypotensive response in ethanol-fed rats than in control rats. Further, blockade of B 2 R with bradyzide (2 mg/kg i.p.) abrogated the enhanced hypotensive effect of enalapril in ethanol-fed rats but had no effect on enalapril-evoked hypotension in control rats. Finally, enalapril enhancement of spontaneous baroreflex sensitivity (BRS) in control was absent in ethanol-fed rats. These findings demonstrate that chronic ethanol produces B 2 R-dependent enhancement of the hypotensive response elicited by enalapril and abrogates enalapril-evoked enhancement of spontaneous baroreflex response in female rats.

Section: Discussionmentioning

confidence: 93%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Bradykinin B2 Receptor–Dependent Enhancement of Enalapril-Evoked Hypotension in Ethanol-Fed Female Rats

Journal of Cardiovascular Pharmacology

Abdel‐Rahman²

2011

“…Plasma estrogen (radioimmunoassay, Diagnostic Systems Laboratories, Inc., Webster, TX), norepinephrine (radioimmunoassay, ALPCO Diagnostics, Windham, NH), ethanol (enzymatic method), and NOx (fluorometric assay, Cayman Chemical Company, Ann Arbor, MI) were determined as described in our previous studies (El-Mas and Abdel-Rahman, 2000, 2001, 2007b; El-Mas et al, 2008). Endotoxin was measured kinetically using a chromogenic test based on the limulus amebocyte lysate (LAL) assay (Kinetic-QCL, BioWhittaker, Walkersville, MD) as described in our previous studies and others (Rivera et al, 1998; El-Mas et al, 2008).…”

Section: Methodsmentioning

confidence: 99%

Upregulation of cardiac NOS due to endotoxemia and vagal overactivity contributes to the hypotensive effect of chronic ethanol in female rats

European Journal of Pharmacology

Fan

Abdel‐Rahman

2011

Self Cite

We previously reported that chronic ethanol lowers blood pressure in female rats. In this study, hemodynamic, biochemical, and immunoblot analyses were performed to investigate: (i) the roles of cardiac contractility and autonomic activity in the hypotensive action of ethanol, and (ii) whether endotoxemia-induced upregulation of cardiac and/or vascular nitric oxide synthase (NOS) isoforms underlies the hypotensive and cardiac effects of ethanol. Telemetric monitoring of blood pressure, heart rate, and myocardial contractility (dP/dt max ) was performed in female rats receiving liquid diet with or without ethanol (5% w/v, 13 weeks). Autonomic control was assessed by frequency domain analysis of interbeat intervals (IBI) and systolic blood pressure (SBP). Compared with pair-fed controls, ethanol caused sustained reductions in blood pressure, heart rate, and +dP/dt max . Ethanol feeding increased the spectral power of high-frequency band (IBI HF , 0.75-3 Hz) and decreased the low-frequency band (IBI LF , 0.25-0.75 Hz) and IBI LF/HF ratio, suggesting increased cardiac parasympathetic dominance. In contrast, vascular tone was not affected by ethanol because SBP spectral bands and plasma norepinephrine remained unchanged. Myocardial expressions of eNOS and its upstream regulators, phosphatidylinositol 3-kinase(PI3K) and Akt, and plasma endotoxin and nitrite/nitrate were increased by ethanol. Myocardial iNOS was also increased by ethanol whereas nNOS remained unchanged and aortic levels of all NOS isoforms were not altered by ethanol. These findings suggest that facilitation of myocardial PI3K/Akt/eNOS and iNOS pathways, due possibly to ethanol-induced endotoxemia and/or increased cardiac parasympathetic dominance, might constitute a cellular mechanism for the reduced myocardial contractility and hypotension caused by ethanol in female rats. KeywordsEthanol; blood pressure; myocardial contractility; female rats; nitric oxide synthase; hemodynamic variability

Cardiovascular autonomic modulation by nitric oxide synthases accounts for the augmented enalapril-evoked hypotension in ethanol-fed female rats

Abdel‐Rahman

2013

Alcohol

Self Cite

In this study, we investigated the role of nitric oxide synthase (NOS) isoforms in the enhanced enalapril-evoked hypotension in ethanol-fed female rats by examining the effect of the selective inhibitors of eNOS [N5-(1-iminoethyl)-L-ornithine; L-NIO], nNOS (Nω-propyl-L-arginine; NPLA), or iNOS (1400W) inhibition on the cardiovascular effects of enalapril in ethanol- (5% w/v) fed rats and in their pair-fed controls In liquid diet-fed control rats, enalapril- (10 mg/kg) evoked hypotension was abolished by L-NIO (20 mg/kg), but not by NPLA (1 mg/kg) or 1400W (5 mg/kg), suggesting a preferential role for eNOS in this response. Enalapril had no effect on spectral indices of hemodynamic variability or +dP/dtmax (myocardial contractility). However, in ethanol-fed rats, the greater enalapril-evoked hypotension was associated with reductions in (i) +dP/dtmax, (ii) low-frequency/high-frequency ratio of interbeat intervals (IBILF/HF), suggesting cardiac parasympathetic dominance, and (iii) low-frequency spectral band of systolic blood pressure (BP), a marker of vasomotor sympathetic tone. While NPLA or 1400W attenuated the enalapril-evoked hemodynamic and autonomic responses in ethanol-fed rats, L-NIO virtually abolished the hypotensive response and was more efficacious in rectifying autonomic responses to enalapril. Together, these findings implicate NOS isoforms, particularly eNOS, in the altered cardiovascular autonomic control that leads to the augmented enalapril-evoked hypotension in ethanol-fed female rats.