Modulation of mean arterial pressure and diuresis by renomedullary infusion of a selective inhibitor of fatty acid amide hydrolase

American Journal of Physiology. Renal Physiology
Ashfaq AhmadJoseph K Ritter

Abstract

The kidneys contribute to the control of body fluid and electrolytes and the long-term regulation of blood pressure through various systems, including the endocannabinoid system. Previously, we showed that inhibition of the two major endocannabinoid-hydrolyzing enzymes, fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase, in the renal medulla increased the rate of urine excretion (UV) and salt excretion without affecting mean arterial pressure (MAP). The present study evaluated the effects of a selective FAAH inhibitor, N-3-pyridinyl-4-[[3-[[5-(trifluoromethyl)-2-pyridinyl]oxy]phenyl]methyl]-1-piperidine carboxamide (PF-3845) on MAP and renal functions. Infusion of PF-3845 into the renal medulla of C57BL/6J mice reduced MAP during the posttreatment phases and increased UV at 15 and 30 nmol/min per gram kidney weight (g kwt), relative to the pretreatment control phase. Intravenous PF-3845 administration reduced MAP at the 7.5, 15, and 30 doses and increased UV at the 15 and 30 nmol⋅min-1⋅g-1 kwt doses. PF-3845 treatment elevated sodium and potassium urinary excretion and medullary blood flow. Homozygous FAAH knockout mice were refractory to intramedullary PF-3845-induced changes in MAP, but UV was increased. Both MAP a...Continue Reading

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Citations

Apr 23, 2020·International Journal of Molecular Sciences·Adam StasiulewiczAnd Joanna I Sulkowska
Mar 13, 2020·Clinical and Experimental Pharmacology & Physiology·Janusz Sadowski, Bożena Bądzyńska
Oct 23, 2020·The Journal of Pharmacology and Experimental Therapeutics·Joseph K RitterVijay Lyall
Aug 23, 2019·Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences·Sara K DempseyJustin L Poklis

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