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

MODULATION OF MEAN ARTERIAL PRESSURE AND DIURESIS BY RENOMEDULLARY INFUSION OF A SELECTIVE INHIBITOR OF FATTY ACID AMIDE HYDROLASE. Am J Physiol Renal Physiol. 2018 May 30;: Authors: Ahmad A, Dempsey SK, Daneva Z, Li N, Poklis JL, Li PL, Ritter JK 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, PF-3845 (N-3-pyridinyl-4-[[3-[[5-(trifluoromethyl)-2-pyridinyl]oxy]phenyl]methyl]-1-piperidine carboxamide) 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/g kwt, relative to the pretreatment control phase. Intravenous administration of PF-3845 reduced MAP at the 7.5, 15 and 30 doses and increased UV at the 15 and 30 nmol/min/g kwt doses. PF-3845 treatment elevated sodium and potassium urinary excretion and MBF. Homozygous FAAH knockout mice were refractory to intramedullary PF-3845- induced changes in MAP, but UV was increased. Both MA...
Source: Am J Physiol Renal P... - Category: Urology & Nephrology Authors: Tags: Am J Physiol Renal Physiol Source Type: research