Clinical and Experimental Nephrology

, Volume 16, Issue 1, pp 17–24 | Cite as

Convergence of major physiological stimuli for renin release on the Gs-alpha/cyclic adenosine monophosphate signaling pathway

  • Soo Mi Kim
  • Josephine P. Briggs
  • Jurgen SchnermannEmail author
Review Article The 36th IUPS Satellite Symposium: The Kidney and Hypertension


Control of the renin system by physiological mechanisms such as the baroreceptor or the macula densa (MD) is characterized by asymmetry in that the capacity for renin secretion and expression to increase is much larger than the magnitude of the inhibitory response. The large stimulatory reserve of the renin–angiotensin system may be one of the causes for the remarkable salt-conserving power of the mammalian kidney. Physiological stimulation of renin secretion and expression relies on the activation of regulatory pathways that converge on the cyclic adenosine monophosphate/protein kinase A (cAMP/PKA) pathway. Mice with selective Gs-alpha (Gsα) deficiency in juxtaglomerular granular cells show a marked reduction of basal renin secretion, and an almost complete unresponsiveness of renin release to furosemide, hydralazine, or isoproterenol. Cyclooxygenase-2 generating prostaglandin E2 (PGE2) and prostacyclin (PGI2) in MD and thick ascending limb cells is one of the main effector systems utilizing Gsα-coupled receptors to stimulate the renin–angiotensin system. In addition, β-adrenergic receptors are critical for the expression of high basal levels of renin and for its release response to lowering blood pressure or MD sodium chloride concentration. Nitric oxide generated by nitric oxide synthases in the MD and in endothelial cells enhances cAMP-dependent signaling by stabilizing cAMP through cyclic guanosine monophosphate-dependent inhibition of phosphodiesterase 3. The stimulation of renin secretion by drugs that inhibit angiotensin II formation or action results from the convergent activation of cAMP probably through indirect augmentation of the activity of PGE2 and PGI2 receptors, β-adrenergic receptors, and nitric oxide.


Cyclooxygenase Nitric oxide synthase Phosphodiesterase Macula densa Baroreceptor ACE inhibition 



The experimental work of the authors was supported by the Intramural Research Program of the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), NIH.


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Copyright information

© Springer 2011

Authors and Affiliations

  • Soo Mi Kim
    • 1
  • Josephine P. Briggs
    • 2
  • Jurgen Schnermann
    • 3
    Email author
  1. 1.Department of PhysiologyChonbuk National University Medical SchoolJeonjuSouth Korea
  2. 2.National Center of Complementary and Alternative Medicine, National Institutes of HealthBethesdaUSA
  3. 3.National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of HealthBethesdaUSA

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