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 AA. Brainstem adenosine A1 receptor signaling masks phosphorylated extracellular signal-regulated kinase 1/2-dependent hypotensive action of clonidine in conscious normotensive rats. JPharmacol Exp Ther 328:83-89, 2009
El-Mas MM and Abdel-Rahman AA. Reduced cardiac contractile force due to sympathovagal dysfunction mediates the additive hypotensive effects of limited-access regimens of ethanol and clonidine in spontaneously hypertensive rats. J Pharmacol Exp Ther, 335 (3), 852-860, 2010.
Bender TS and Abdel-Rahman AA. Differential Central NOS-NO Signaling Underlies Clonidine Exacerbation of Ethanol-Evoked Behavioral Impairment. Alcohol: Clinical &Experimental Research, 34 (3), 555-566, 2010.
El-Mas MM and Abdel-Rahman AA. Upregulation of cardiac NOS due to endotoxemia and vagal overactivity contributes to the hypotensive effect of chronic ethanol in female rats. European J. Pharmacology, 650 (1), 317-323, 2011.
El-Mas, M., El-Gowelli, H., Abd-Elrahman, K., Saad, E., Abdel-Rahman, AA, Abdel-Galil, AG. Pioglitazone abrogates cyclosporine-evoked hypertension via rectifying abnormalities in vascular endothelial function. Biochemical Pharmacology, 81 (4),526-533, 2011.
Ibrahim BM, Abdel-Rahman AA. Role of brainstem GABAergic signaling in central cannabinoid receptor evoked sympathoexcitation 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, AA. Estrogen dependence of the renal vasodilatory effect of nicotine in rats: role of ±7 nicotinic cholinergic receptor/eNOS signaling. Life Sciences, 88 (3-4), 187-193, 2011.
El-Mas, M. and Abdel-Rahman, AA. Bradykinin b2 receptor-dependent enhancement of enalapril-evoked hypotension in ethanol-fed female rats. J Cardiovascular Pharmacology, 57(1), 72-80, 2011.
Stabile, A., Aceros, H., Stockmeyer, K., Abdel-Rahman, AA., Noiseux, N., Mukaddam-Daher S. Functional and molecular effects of imidazoline receptor activation in heart failure. LifeSciences, 88(3-4):187-93,2011
El-Mas MM and Abdel-Rahman AA. Upregulation of cardiac NOS due to endotoxemia and vagal overactivity contributes to the hypotensive effect of chronic ethanol in female rats. Eur J Pharmacol. 650(1):317-23, 2011
McGee MA, Abdel-Rahman AA. Enhanced vascular neuronal nitric-oxide synthase-derived nitricoxide production underlies the pressor effect caused by peripheral N-methyl-D-aspartate receptor activation in conscious rats. J Pharmacol Exp Ther. 342(2):461-71, 2012
Ibrahim BM, Abdel-Rahman AA. Enhancement of rostral ventrolateral medullaneuronal nitric-oxide synthase-nitric-oxide signaling mediates the central cannabinoid receptor 1-evoked pressor response in conscious rats. J Pharmacol Exp Ther.,341(3):579-86, 2012.
El-Mas MM, Abdel-Rahman AA. Exacerbation of myocardial dysfunction and autonomic imbalance contributes to the estrogen-dependent chronic hypotensive effect of ethanol in female rats. Eur J Pharmacol.;679(1-3):95-100, 2012
El-Mas MM, Abdel-Rahman AA. Enhanced catabolism to acetaldehyde in rostral ventrolateral medullary neurons accounts for the pressor effect of ethanol in spontaneously hypertensive rats. Am J Physiol Heart Circ Physiol. 302(3):H837-44, 2012
Ibrahim BM, Abdel-Rahman AA. Differential modulation of brainstem phosphatidylinositol 3-kinase/Akt and extracellular signal-regulated kinase ½signaling underlies WIN55,212-2 centrally mediated pressor response in conscious rats. J Pharmacol Exp Ther;340(1):11-8, 2012
El-Mas MM, Abdel-Rahman AA. Cardiovascular autonomic modulation by nitric oxide synthases accounts for the augmented enalapril-evoked hypotension in ethanol-fed female rats. Alcohol 47(4):339-46, 2013
El-Mas MM, Fan M and Abdel-Rahman AA. Role of Rostral Ventrolateral Medullary ERK/JNK/p38 MAPK Signaling in the Pressor 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 AA. Enhanced Vascular PI3K/Akt-NOX Signaling Underlies the Peripheral NMDAR-Mediated Pressor Response in Conscious Rats. J Cardiovascular Pharm. 63(5):395-405, 2014
Penumarti A and Abdel-Rahman AA. The Novel Endocannabinoid Receptor GPR18 is Expressed in the Rostral Ventrolateral Medulla and Exerts Tonic Restraining Influence on Blood Pressure. J Pharmacol Exp Ther. 349(1):29-38, 2014
Ibrahim BM, Fan M and Abdel-Rahman AA. Oxidative stress and autonomic dysregulation contribute to the acute time-dependent myocardial depressant effect of ethanol in conscious female rats. Alcoholism: Clin ExpRes. 38(5):1205-15, 2014
Ibrahim BM and Abdel-Rahman AA. Cannabinoid receptor 1 signaling in cardiovascular regulating nuclei in the brainstem: A review. J Advanced Res.5:137-145, 2014
El-Mas MM, Abdel-Rahman AA. Endothelial and neuronal nitric oxide synthases variably modulate the oestrogen-mediated control of blood pressure and cardiovascular autonomic control. Clin Exp Pharmacol Physiol.41(3):246-54, 2014
Taki, FA, Abdel-Rahman AA, Zhang, B. A Comprehensive Approach to Identify Reliable Reference Gene Candidates to Investigate the Link between Alcoholism and Endocrinology in Sprague-Dawley Rats. PLOS ONE 9:1-15, 2014
El-Mas MM, Abdel-Rahman AA. Nongenomic effects of estrogen mediate the dose-related myocardial oxidative stress and dysfunction caused by acute ethanol in female rats. Am J Physiol Endocrinol Metab. 306(7): E740-747, 2014
El-Mas MM, Abdel-Rahman AA.Ser/thr phosphatasestonically attenuate the ERK-dependent pressor effect of ethanol in the rostral ventrolateral medulla in normotensive rats. Brain Res. 19;1577:21-8;2014
Penumarti A, Abdel-Rahman AA. Neuronal nitric oxide synthase-dependent elevation in adiponectin in the rostral ventrolateral medulla underlies g protein-coupled receptor 18-mediated hypotension in conscious rats.J Pharmacol Exp Ther;351(1):44-53, 2014
Ibrahim BM, Abdel-Rahman AA. A pivotal role for enhanced brainstem Orexin receptor 1 signaling in the central cannabinoid receptor 1-mediated pressor response in conscious rats. Brain research. 2015;PubMed [journal]PMID: 26096126
El-Mas MM, Abdel-Rahman AA. Estrogen modulation of the ethanol-evoked myocardial oxidative stress and dysfunction via 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 stress and pressor response. Alcohol (Fayetteville, N.Y.) 2015;49(5):499-506.PubMed [journal] PMID: 25986731 PMCID: PMC4469563
Kui Sun, Research Specialist
Rebecca Steagall, Post Doctoral Fellow
Fanrong Yao, Post Doctoral Fellow
Samar Rezq, Graduate Student