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ADPR cyclase and ryanodine receptors participate in regulation of basal renal blood flow and vasoconstriction induced by Bay‐K8644 in vivo
Author(s) -
Thai Tiffany L,
Arendshorst William J
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a499
Subject(s) - ryanodine receptor , vasoconstriction , endocrinology , medicine , bay k8644 , chemistry , receptor , biology , agonist
Renal vasoconstriction is mediated by increases in cytosolic calcium ([Ca 2+ ] i ). ADP ribosyl cyclase (ADPR cycles) activation leads to formation of cyclic ADP ribose (cADPR) and/or nicotinic acid ADP (NAADP), both of which activate ryanodine receptors (RyR) on the sarcoplasmic reticulum to release Ca 2+ . We tested the hypothesis that basal activity of ADPR cyclase and RYRs participate in regulation of renal blood flow (RBF) in vivo. Using an ultrasonic flow transducer, we continuously measured RBF in anesthetized Sprague‐Dawley rats. Nicotinamide, an ADPR cyclase inhibitor, infused into the renal artery, increased basal RBF by 22% (P<0.001) without affecting arterial pressure. To determine if RyRs participate in contraction, we injected FK506, a peptide known to stimulate RyRs by a mechanism similar to cADPR, intrarenally. FK506 decreased RBF by 22% (P<0.02), indicating that RyRs are present and act significantly in RBF control. We also tested whether ADPR cyclase and RyRs function in amplification of Ca 2+ responses using the L type Ca 2+ channel agonist Bay‐K8644 to reduce RBF. Responses to Bay‐K8644 were attenuated 59% (P=0.01) by nicotinamide and 63% (P<0.001) by the RyR inhibitor ruthenium red. Collectively, our results demonstrate that baseline ADPR cyclase and RyR activities play important roles in control of resting renal vasomotor tone and amplification of Ca 2+ ‐induced renal vasoconstriction in vivo.