Regulation of the renal microcirculation by ryanodine receptors and calcium-induced calcium release.
OBJECTIVE
Emerging evidence highlights the importance of physiological participation of ryanodine receptors (RyR) and Ca-induced-Ca-release (CICR) from the sarcoplasmic reticulum in Ca signaling and arteriolar contraction in the renal microcirculation.


RESULTS
Adenosine diphosphate -ribosyl (ADPR) cyclase and its endogenous metabolites cyclic adenosine diphosphate-ribose and nicotinic acid adenine dinucleotide phosphate mobilize intracellular Ca 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 Ca concentration ([Ca]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 [Ca]i responses initiated by Ca entry and by inositol trisphosphate receptor-induced sarcoplasmic reticulum Ca release. Acute [Ca]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.


CONCLUSIONS
RyR and CICR are important regulations of Ca signaling and contractile tone of renal resistance arterioles in healthy kidneys. The role of this novel-signaling pathway in pathophysiological mechanisms awaits investigation.
Arendshorst
William J
WJ
Department of Cell and Molecular Physiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA. arends@med.unc.edu
Thai
Tiffany L
TL
D036541:ADP-ribosyl Cyclase / Q000502:physiology; D000818:Animals; D002118:Calcium / Q000378:metabolism* / Q000494:pharmacology*; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D008833:Microcirculation / Q000187:drug effects; D032389:Myocytes, Smooth Muscle / Q000187:drug effects; D009569:Nitric Oxide / Q000378:metabolism; D012079:Renal Circulation / Q000187:drug effects*; D019837:Ryanodine Receptor Calcium Release Channel / Q000187:drug effects*; D015290:Second Messenger Systems / Q000187:drug effects
D015220:Calcium Channels; D019837:Ryanodine Receptor Calcium Release Channel; D009569:Nitric Oxide; D036541:ADP-ribosyl Cyclase; D002118:Calcium