Regulation of the renal microcirculation by ryanodine receptors and calcium-induced calcium release.

PURPOSE OF REVIEW: 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. RECENT
FINDINGS: 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.
CONCLUSION: 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.