Attenuation by alpha,beta-methylenadenosine-5'-triphosphate of periarterial nerve stimulation-induced renal vasoconstriction is not due to desensitization of purinergic receptors.
We investigated in the isolated rat kidney the modulation of vasoconstrictor responses to ATP (0.05-0.5 mumol), renal nerve stimulation (RNS) (0.5-10.0 Hz), norepinephrine (NE) (0.15-0.9 nmol), angiotensin II (2 pmol) and arginine vasopressin (3 pmol) by alpha,beta-methylenadenosine-5'-triphosphate (alpha beta mATP) infused at 6 microM (Procedure I) or for short intervals (5 min) at a low concentration (60 nM) gradually increased to 6 microM to reduce the dramatic initial vasoconstriction (Procedure II). Infusion of alpha beta mATP (Procedure I) produced a marked, transient rise in perfusion pressure of 146 to 198 mm Hg that returned to basal level within 10 min and thereafter inhibited the vasoconstrictor response to ATP, RNS (0.5-6.0 Hz), NE, angiotensin II and arginine vasopressin. Infusion of alpha beta mATP by Procedure II produced a smaller maximal transient increase in perfusion pressure (< 100 mm Hg) and reduced the vasoconstrictor responses to RNS at 0.5 to 2.0 Hz and to the lower dose of NE (0.15 nmol) only. ATP infusion reduced the vasoconstrictor response to both RNS and NE. In animals pretreated with reserpine, the effect of RNS to produce vasoconstriction was inhibited. These data suggest that ATP does not contribute to the renal vasoconstrictor response elicited by RNS, and that attenuation of renal vasoconstrictor responses by alpha beta mATP is not due to desensitization of purinergic receptors.
Department of Pharmacology, College of Medicine, University of Tennessee, Memphis 38163.
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Sehic
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Ruan
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Malik
D000255:Adenosine Triphosphate / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D004558:Electric Stimulation; D007668:Kidney / Q000187:drug effects* / Q000294:innervation / Q000502:physiology; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology; D010477:Perfusion; D051381:Rats; D017207:Rats, Sprague-Dawley; D018048:Receptors, Purinergic P2 / Q000187:drug effects*; D012110:Reserpine / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects*
D018048:Receptors, Purinergic P2; D012110:Reserpine; D000255:Adenosine Triphosphate; C002630:alpha,beta-methyleneadenosine 5'-triphosphate; D009638:Norepinephrine