Juxtamedullary afferent arteriolar responses to P1 and P2 purinergic stimulation.
We assessed the responsiveness of rat juxtamedullary afferent arterioles to purinergic stimulation using the in vitro blood-perfused juxtamedullary nephron technique combined with videomicroscopy to allow direct measurement of arteriolar inside diameter. To minimize the contribution of endogenously formed angiotensin II, all rats were pretreated with enalaprilat (2 mg i.v.) for 30 minutes before the right kidney was isolated and prepared for study. Renal perfusion pressure was set at 110 mm Hg and held constant. Afferent arteriolar diameter averaged 20.9 +/- 0.8 microns (n = 41) under control conditions. Exposure to 1.0 microM 2-chloroadenosine induced a significant (11.1 +/- 3.2%) reduction in vessel diameter, whereas a 100 microM concentration induced an afferent vasodilation (7.6 +/- 1.5%; p less than 0.05). These data are consistent with the preferential stimulation of high affinity constrictor adenosine receptors (A1) at lower concentrations and activation of lower affinity vasodilator adenosine receptors (A2) at higher concentrations. In contrast, ATP elicited a significant afferent vasoconstriction of approximately 9.2%, 12.9%, and 10.0% at concentrations in the range of 1-100 microM (p less than 0.05). Treatment with ADP, at concentrations up to 100 microM, failed to alter vessel caliber significantly. Furthermore, the nonhydrolyzable ATP analogue alpha,beta-methylene ATP produced a rapid and potent vasoconstriction, which mimicked the response to ATP. These data reveal the presence of both adenosine-sensitive P1 and ATP-sensitive P2 purinergic receptors on rat juxtamedullary afferent arterioles and demonstrate that ATP can induce afferent arteriolar vasoconstriction directly without first requiring hydrolysis to adenosine.
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Department of Physiology, Tulane University School of Medicine, New Orleans, LA 70112.
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D015762:2-Chloroadenosine / Q000494:pharmacology; D000244:Adenosine Diphosphate / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D001160:Arterioles / Q000187:drug effects / Q000502:physiology; D008297:Male; D011687:Purines / Q000378:metabolism*; D051381:Rats; D012079:Renal Circulation / Q000187:drug effects / Q000502:physiology*; D013997:Time Factors; D014661:Vasoconstriction
D011687:Purines; D015762:2-Chloroadenosine; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; C002630:alpha,beta-methyleneadenosine 5'-triphosphate