title: Brain stem adenosine receptors modulate centrally mediated hypotensive responses in conscious rats: A review.
abstract: Adenosine is implicated in the modulation of cardiovascular responses either at the peripheral or at central level in experimental animals. However, there are no dedicated reviews on the involvement of adenosine in mediating the hypotensive response of centrally administered clonidine in general and specifically in aortically barodenervated rats (ABD). The conscious ABD rat model exhibits surgically induced baroreflex dysfunction and exaggerated hypotensive response, compared with conscious sham-operated (SO) rats. The current review focuses on, the role of adenosine receptors in blood pressure (BP) regulation and their possible crosstalk with other receptors e.g. imidazoline (I1) and alpha (α2A) adrenergic receptor (AR). The former receptor is a molecular target for clonidine, whose hypotensive effect is enhanced approx. 3-fold in conscious ABD rats. We also discussed how the balance between the brain stem adenosine A1 and A2A receptors is regulated by baroreceptors and how such balance influences the centrally mediated hypotensive responses. The use of the ABD rat model yielded insight into the downstream signaling cascades following clonidine-evoked hypotension in a surgical model of baroreflex dysfunction.
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Pharmacy, Cairo University, Egypt.
authors.forename: Noha N
authors.initials: NN
authors.lastname: Nassar
authors.affiliation: Department of Pharmacology and Toxicology, Brody School of Medicine, East Carolina University, NC, USA.
authors.forename: Abdel A
authors.initials: AA
authors.lastname: Abdel-Rahman
keywords: 8-SPT, 8-(p-sulfophenyl)-theophylline. Non-selective adenosine receptor blocker; A1, adenosine subtype A1 receptor; A2A, adenosine subtype A2A receptor; ABC, avidin biotin complex; ABD rat, aortic barodenervated rat; ATP, adenosine triphosphate; BP, blood pressure; CGS21680, 2-[4-[(2-carboxyethyl)phenyl]ethylaminophenyl]ethylamino]-5′-N-ethylcarboxamidoadenosine. Selective A2A receptor agonist; CNS, central nervous system; CPA, N6-cyclopentyladenosine. Selective A1 receptor agonist; Central adenosine receptors; Centrally mediated hypotension; Clonidine; Conscious rats; DAG, diacylglycerol; DPCPX, 8-cyclopentyl-1,3-dipropylxanthine. Selective A1 receptor antagonist; ERK1/2, extracellular signal regulated kinase; I.C., intracisternal; I.V., intravenous; I1, imidazoline subtype 1 receptor; IP3, Inositol Triphosphate; Imidazoline I1-receptor; JNK, C-Jun N-terminal kinase; L-NAME, Nω-nitro-l-arginine methyl ester hydrochloride. Non-selective nitric oxide synthase inhibitor; MAPK-NOS signaling; NO, nitric oxide; NOS, nitric oxide synthase; NTS, nucleus tractus solitarius; PC-PLC, phosphatidyl choline-selective phospholipase C; PC12 cells, pheochromocytoma cells; PD98059, selective extracellular signal regulated kinase inhibitor; PDE, phosphodiesterase; PKA, protein kinase A; RVLM, rostral ventrolateral medulla; SAPK, stress activated protein kinase; SCH58261, 5-amino-7-(2-phenylethyl)-2-(2-furyl)-pyrazolo[4,3-[Formula: see text]]-1,2,4-triazolo[1,5-c]pyrimidine. Selective adenosine A2A antagonist; SHR, spontaneously hypertensive rat; SND, sympathetic neuronal discharge; SO, sham operated = conscious normotensive rats; WKY, Wistar Kyoto rat; cAMP, cyclic adenosine monophosphate; α2 AR, alpha 2 adrenergic receptor; αMNE, alpha methyl norepinephrine