title: Role of NO and COX pathways in mediation of adenosine A1 receptor-induced renal vasoconstriction.
abstract: The mechanism of adenosine A1 receptor-induced intrarenal vasoconstriction is unclear; it depends on sodium intake and may be mediated by changing the intrarenal activity of the nitric oxide (NO) and/or cyclooxygenase (COX) pathway of arachidonic acid metabolism. The effects of 2-chloro-N(6)-cyclopentyl-adenosine (CCPA), a selective A1 receptor agonist, on renal hemodynamics were examined in anesthetized rats maintained on high sodium (HS) or low sodium (LS) diet. Total renal (i.e., cortical) blood flow (RBF) as well as superficial cortical (CBF), outer medullary (OMBF), and inner medullary (IMBF) flows were determined by laser-Doppler. In HS rats, suprarenal aortic infusions of 8-40 nmol/kg/hr CCPA decreased IMBF (15%) and other perfusion indices (22%-27%); in LS rats, IMBF increased 3% (insignificant) and other indices decreased 13%-24%. In LS rats, pretreatment with N-nitro-L-arginine methyl ester prevented the A1 receptor-mediated decrease in RBF and CBF but not OMBF; the response in IMBF was not altered. Pretreatment with indomethacin prevented the decreases in RBF, CBF, and OMBF and did not change the response of IMBF. Thus, within the cortex the vasoconstriction that follows A1 receptor activation results both from inhibition of NO synthesis and from stimulation of vasoconstrictor products of the COX pathway. In the outer medulla, the latter products seem exclusively responsible for CCPA-induced vasoconstriction. The observation that in LS rats IMBF was not affected by stimulation of adenosine A1 receptors suggests that limiting salt intake may help protect medullary perfusion against vasoconstrictor stimuli which have the potential to disturb long-term control of arterial pressure.
authors.affiliation: Laboratory of Renal and Body Fluid Physiology, M. Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland. renal@cmdik.pan.pl
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Walkowska
authors.forename: Leszek
authors.initials: L
authors.lastname: Dobrowolski
authors.forename: Elzbieta
authors.initials: E
authors.lastname: Kompanowska-Jezierska
authors.forename: Janusz
authors.initials: J
authors.lastname: Sadowski
mesh_terms: D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology; D058907:Adenosine A1 Receptor Agonists; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007668:Kidney / Q000098:blood supply*; D007672:Kidney Cortex / Q000098:blood supply; D007679:Kidney Medulla / Q000098:blood supply; D017078:Laser-Doppler Flowmetry; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D043682:Receptor, Adenosine A1 / Q000502:physiology*; D012079:Renal Circulation / Q000187:drug effects; D015398:Signal Transduction / Q000502:physiology*; D012982:Sodium, Dietary / Q000008:administration & dosage; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology*
chemical_list: D058907:Adenosine A1 Receptor Agonists; D004791:Enzyme Inhibitors; D043682:Receptor, Adenosine A1; D012982:Sodium, Dietary; D009569:Nitric Oxide; C058394:2-chloro-N(6)cyclopentyladenosine; D019001:Nitric Oxide Synthase; D011451:Prostaglandin-Endoperoxide Synthases; D000241:Adenosine; D019331:NG-Nitroarginine Methyl Ester