Activation of the cannabinoid receptor 2 increases renal perfusion

J. D. Pressly, H. Soni, S. Jiang, J. Wei, R. Liu, B. M. Moore, Adebowale Adebiyi, Frank Park

Research output: Contribution to journalArticle

Abstract

First published February 1, 2019; doi:10.1152/physiolgenomics.00001.2019.— Acute kidney injury (AKI) is an increasing clinical problem that is associated with chronic kidney disease progression. Cannabinoid receptor 2 (CB2) activation has been shown to mitigate some of the deleterious tubular effects due to AKI, but its role on the renal vasculature has not been fully described. In this study, we investigated the effects of our novel CB2 receptor agonist, SMM-295, on renal vasculature by assessing cortical perfusion with laser Doppler flow-metry and changes in luminal diameter with isolated afferent arterioles. In this study, intravenously infused SMM-295 (6 mg/kg) significantly increased cortical renal perfusion (13.8 ± 0.6%; P < 0.0001; n = 7) compared with vehicle (0.1 ± 1.5%; n = 10) normalized to baseline values in anesthetized C57BL/6J mice. This effect was not dependent upon activation of the CB1 receptor (met-anandamide; 6 mg/kg iv) and was predominantly abolished in Cnr2 knockout mice with SMM-295 (6 mg/kg iv). Ablation of the renal afferent nerves with capsaicin blocked the SMM-295-dependent increase in renal cortical perfusion, and the increased renal blood flow was not dependent upon products synthesized by cyclooxygenase or nitric oxide synthase. The increased renal perfusion by CB2 receptor activation is also attributed to a direct vascular effect, since SMM-295 (5 ųM) engendered a significant 37 ± 7% increase (P < 0.0001; n = 4) in luminal diameters of norepinephrine-preconstricted afferent arterioles. These data provide new insight into the potential benefit of SMM-295 by activating vascular and nonvascular CB2 receptors to promote renal vasodilation, and provide a new therapeutic target to treat renal injuries that impact renal blood flow dynamics.

Original languageEnglish (US)
Pages (from-to)90-96
Number of pages7
JournalPhysiological genomics
Volume51
Issue number3
DOIs
StatePublished - Mar 1 2019

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Cannabinoid Receptors
Perfusion
Kidney
Renal Circulation
Arterioles
Acute Kidney Injury
Blood Vessels
Cannabinoid Receptor CB1
Capsaicin
Prostaglandin-Endoperoxide Synthases
Chronic Renal Insufficiency
Inbred C57BL Mouse
Knockout Mice
Vasodilation
Nitric Oxide Synthase
Disease Progression
Norepinephrine
Lasers
Wounds and Injuries

All Science Journal Classification (ASJC) codes

  • Physiology
  • Genetics

Cite this

Activation of the cannabinoid receptor 2 increases renal perfusion. / Pressly, J. D.; Soni, H.; Jiang, S.; Wei, J.; Liu, R.; Moore, B. M.; Adebiyi, Adebowale; Park, Frank.

In: Physiological genomics, Vol. 51, No. 3, 01.03.2019, p. 90-96.

Research output: Contribution to journalArticle

Pressly, J. D. ; Soni, H. ; Jiang, S. ; Wei, J. ; Liu, R. ; Moore, B. M. ; Adebiyi, Adebowale ; Park, Frank. / Activation of the cannabinoid receptor 2 increases renal perfusion. In: Physiological genomics. 2019 ; Vol. 51, No. 3. pp. 90-96.
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