Circulation and hemodynamics: Edited by Roland C. Blantz and Matthew R. WeirRegulation of the renal microcirculation by ryanodine receptors and calcium-induced calcium releaseArendshorst, William J; Thai, Tiffany LAuthor Information Department of Cell and Molecular Physiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA Correspondence to William J. Arendshorst, PhD, Department of Cell and Molecular Physiology, CB # 7545, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7545, USA Tel: +1 919 966 1067; fax: +1 919 966 6927; e-mail: [email protected] Current Opinion in Nephrology and Hypertension: January 2009 - Volume 18 - Issue 1 - p 40-49 doi: 10.1097/MNH.0b013e32831cf5bd Buy Metrics Abstract Purpose of review Emerging evidence highlights the importance of physiological participation of ryanodine receptors (RyR) and Ca2+-induced-Ca2+-release (CICR) from the sarcoplasmic reticulum in Ca2+ signaling and arteriolar contraction in the renal microcirculation. Recent findings Adenosine diphosphate -ribosyl (ADPR) cyclase and its endogenous metabolites cyclic adenosine diphosphate-ribose and nicotinic acid adenine dinucleotide phosphate mobilize intracellular Ca2+ from sarcoplasmic reticulum stores in the renal vasculature via actions on RyR. The ADPR cyclase/cyclic adenosine diphosphate-ribose/RyR/CICR second messenger system mediates significant (>50%) changes in cytosolic Ca2+ concentration ([Ca2+]i) and contractile function of preglomerular arteries/arterioles during angiotensin II and endothelin-1 stimulation of G-protein coupled receptors. These receptors rapidly activate ADPR cyclase via stimulation of superoxide (O2−) production by nicotinamide adenine dinucleotide phosphate oxidases. Basal ADPR cyclase activity and RyR/CICR contribute to [Ca2+]i responses initiated by Ca2+ entry and by inositol trisphosphate receptor-induced sarcoplasmic reticulum Ca2+ release. Acute [Ca2+]i responses in isolated afferent arterioles and renal vasoconstriction in vivo are attenuated by more than 50% by pharmacological inhibition of ADPR cyclase or RyR. Similarly, renal vascular reactivity to angiotensin II, endothelin-1 and norepinephrine is attenuated by approximately 50% in mice lacking CD38, the main mammalian ADPR cyclase. Conclusion RyR and CICR are important regulations of Ca2+ signaling and contractile tone of renal resistance arterioles in healthy kidneys. The role of this novel-signaling pathway in pathophysiological mechanisms awaits investigation. © 2009 Lippincott Williams & Wilkins, Inc.