Research pursued in our laboratory covers two areas, neuroscience/neuropharmacology and cardiovascular biology/pharmacology. A common theme of our research program is the elucidation of the molecular mechanisms that promote and suppress oxidative stress in cardiovascular tissues as well as in brain nuclei that control sympathetic activity and blood pressure. Our research findings have provided important basic and clinically relevant knowledge in well-established models of human pathophysiology. Recent research directions focus on why alterations in cellular environment transform the cardioprotective estrogen into a proinflammatory hormone that promotes myocardial injury. Such studies cover a myriad of molecular studies on estrogen receptor subtype signaling and trafficking in animal models of surgical menopause. We are currently extending our novel findings on altered phospholipid metabolism in hypertension to understand the roles of abnormal phospholipid generation in mitochondrial and myocardial dysfunction following binge pattern alcohol consumption. Finally, we conduct comprehensive studies on central and cardiovascular cannabinoid receptor signaling and the therapeutic potential of targeting this rapidly developing system for the treatment of human diseases such as hypertension and diabetes. Continuous NIH funding has permitted acquisition of important equipment needed for our multilevel approach research. We routinely add new methodologies and enlist valuable collaborations to enhance our capabilities of conducting cutting edge NIH-funded research in a rapidly developing area of investigation.
Some specific areas of interest:
1. Negative impact of alcohol on central hemeoxygenase and catalase regulation of blood pressure and heart rate in hypertension
2. Molecular mechanisms of estrogen-dependent oxidative stress and myocardial injury caused by alcohol
3. The importance of phospholipid metabolism (phosphatidic acid) in preserving left ventricular function during the compensated phase of the hypertensive heart
4. The molecular interaction between the classic cannabinoid (CB1)receptor and the novel cannabinoid receptor GPR18 determines the neuronal redox state and blood pressure
5. The role of hydrogen sulfide in the favorable glycemic and cardiovascular effects of imidazoline receptor activation in diabetic rats
6. The role of lipid rafts and their major protein caveolin in estrogen receptor and cannabinoid receptors trafficking and signaling in neurons and cardiac myocytes
Nassar NN and Abdel-Rahman A-R.A. Brainstem adenosine A1 receptor signaling masksphosphorylated extracellular signal-regulated kinase 1/2-dependent hypotensiveaction of clonidine in conscious normotensive rats. JPharmacol Exp Ther 328:83-89, 2009
El-Mas MM and Abdel-Rahman A-R. A.Reducedcardiac contractile force due to sympathovagal dysfunction mediates theadditive hypotensive effects of limited-access regimens of ethanol andclonidine in spontaneously hypertensive rats. J PharmacolExp Ther, 335 (3), 852-860, 2010.
BenderTS and Abdel-Rahman A-R.A.DifferentialCentral NOS-NO Signaling Underlies Clonidine Exacerbation of Ethanol-Evoked BehavioralImpairment. Alcohol: Clinical &Experimental Research,34 (3), 555-566, 2010.
El-Mas MM and Abdel-Rahman A-R. A.Upregulationof cardiac NOS due to endotoxemia and vagal overactivity contributes to thehypotensive effect of chronic ethanol in female rats. EuropeanJ. Pharmacology, 650 (1), 317-323, 2011.
El-Mas, M.,El-Gowelli, H., Abd-Elrahman, K., Saad, E., Abdel-Rahman, A-R. A, Abdel-Galil, AG. Pioglitazone abrogatescyclosporine-evoked hypertension via rectifying abnormalities in vascularendothelial function. Biochemical Pharmacology, 81 (4),526-533, 2011.
IbrahimBM, Abdel-Rahman AA. Role ofbrainstem GABAergic signaling in central cannabinoid receptor evokedsympathoexcitation and pressor responses in conscious rats. BrainRes, 26;1414:1-9, 2011
El-Mas, M.,El-Gowilly, S., Gohar, E., Ghazal, A., and Abdel-Rahman,A-R.A. Estrogen dependence of the renal vasodilatory effect ofnicotine in rats: role of ±7 nicotinic cholinergic receptor/eNOSsignaling. Life Sciences, 88 (3-4), 187-193, 2011.
El-Mas, M. andAbdel-Rahman, A-R.A. Bradykinin b2 receptor-dependent enhancement of enalapril-evoked hypotension inethanol-fed female rats. J Cardiovascular Pharmacology, 57(1), 72-80, 2011.
Stabile, A.,Aceros, H., Stockmeyer, K., Abdel-Rahman,A-R. A., Noiseux, N., Mukaddam-Daher S. Functional and moleculareffects of imidazoline receptor activation in heart failure. LifeSciences, 88(3-4):187-93,2011
El-Mas MM,and Abdel-Rahman A-R A. Upregulation of cardiac NOS due toendotoxemia and vagal overactivity contributes to the hypotensive effect ofchronic ethanol in female rats. Eur J Pharmacol. 650(1):317-23, 2011
McGee MA, Abdel-RahmanA-R A. Enhanced vascular neuronal nitric-oxide synthase-derived nitricoxide production underlies the pressor effect caused by peripheralN-methyl-D-aspartate receptor activation in conscious rats. JPharmacol Exp Ther. 342(2):461-71, 2012
Ibrahim BM, Abdel-RahmanA-R A.Enhancement of rostral ventrolateral medullaneuronal nitric-oxide synthase-nitric-oxide signaling mediates the centralcannabinoid receptor 1-evoked pressor response in conscious rats. JPharmacol Exp Ther.,341(3):579-86, 2012.
El-Mas MM, Abdel-RahmanA-R A. Exacerbation of myocardial dysfunction and autonomic imbalancecontributes to the estrogen-dependent chronic hypotensive effect of ethanol infemale rats. Eur J Pharmacol.;679(1-3):95-100, 2012
El-Mas MM, Abdel-RahmanA-R A.Enhanced catabolism toacetaldehyde in rostral ventrolateral medullary neurons accounts for thepressor effect of ethanol in spontaneously hypertensive rats. Am JPhysiol Heart Circ Physiol. 302(3):H837-44, 2012
Ibrahim BM, Abdel-Rahman A-R A. Differential modulation of brainstemphosphatidylinositol 3-kinase/Akt and extracellular signal-regulated kinase ½signaling underlies WIN55,212-2 centrally mediated pressor response inconscious rats. J Pharmacol Exp Ther;340(1):11-8, 2012
El-MasMM, Abdel-Rahman A-R A. Cardiovascular autonomic modulation by nitricoxide synthases accounts for the augmented enalapril-evoked hypotension inethanol-fed female rats. Alcohol 47(4):339-46, 2013
El-MasMM, Fan M and Abdel-Rahman A-R A.Role of Rostral Ventrolateral Medullary ERK/JNK/p38 MAPK Signaling in thePressor Effects of Ethanol and Its Oxidative Product Acetaldehyde. Alcohol Clin Exp Res. Alcohol Clin ExpRes. 37(11):1827-37, 2013
McGee M and Abdel-Rahman A-R A. Enhanced Vascular PI3K/Akt-NOXSignaling Underlies the Peripheral NMDAR-Mediated Pressor Response in ConsciousRats. J Cardiovascular Pharm. 63(5):395-405, 2014
Penumarti A and Abdel-Rahman A-R A. The Novel Endocannabinoid Receptor GPR18 isExpressed in the Rostral Ventrolateral Medulla and Exerts Tonic RestrainingInfluence on Blood Pressure. J Pharmacol Exp Ther. 349(1):29-38, 2014
Ibrahim BM, Fan M and Abdel-RahmanA-R A. Oxidative stress andautonomic dysregulation contribute to the acute time-dependent myocardialdepressant effect of ethanol in conscious female rats. Alcoholism: Clin ExpRes. 38(5):1205-15, 2014
Ibrahim BM and Abdel-Rahman A-R A. Cannabinoid receptor 1 signaling incardiovascular regulating nuclei in the brainstem: A review. J Advanced Res.5:137-145, 2014
El-Mas MM, Abdel-Rahman A-R A. Endothelialand neuronal nitric oxide synthases variably modulate the oestrogen-mediatedcontrol of blood pressure and cardiovascular autonomic control. Clin Exp Pharmacol Physiol.41(3):246-54, 2014
Taki, FA, Abdel-Rahman A-R A, Zhang, B. A Comprehensive Approach toIdentify Reliable Reference Gene Candidates to Investigate the Link betweenAlcoholism and Endocrinology in Sprague-Dawley Rats. PLOS ONE 9:1-15, 2014
El-Mas MM, Abdel-Rahman A-R A. Nongenomiceffects of estrogen mediate the dose-related myocardial oxidative stress anddysfunction caused by acute ethanol in female rats. Am J Physiol Endocrinol Metab. 306(7):E740-747, 2014
El-Mas MM, Abdel-Rahman A-R A.Ser/thr phosphatasestonically attenuate the ERK-dependent pressor effect of ethanol in the rostralventrolateral medulla in normotensive rats. Brain Res. 19;1577:21-8;2014
Penumarti A, Abdel-RahmanAA.Neuronal nitric oxide synthase-dependent elevation in adiponectin in therostral ventrolateral medulla underlies g protein-coupled receptor 18-mediatedhypotension in conscious rats.J Pharmacol Exp Ther;351(1):44-53, 2014
Ibrahim BM, Abdel-Rahman AA. A pivotal rolefor enhanced brainstem Orexin receptor 1 signaling in the central cannabinoidreceptor 1-mediated pressor response in conscious rats. Brain research. 2015;PubMed [journal]PMID: 26096126
El-Mas MM, Abdel-Rahman AA. Estrogenmodulation of the ethanol-evoked myocardial oxidative stress and dysfunctionvia DAPK3/Akt/ERK activation in male rats. Toxicology and applied pharmacology.2015;PubMed [journal] PMID: 26111663
McGee MA, Abdel-Rahman AA. Ethanol attenuates peripheral NMDAR-mediated vascular oxidative stressand pressor response. Alcohol (Fayetteville, N.Y.) 2015;49(5):499-506.PubMed [journal] PMID: 25986731 PMCID: PMC4469563