Role of NO and COX pathways in mediation of adenosine A1 receptor-induced renal vasoconstriction.

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.