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Am J Physiol Renal Physiol (March 18, 2003). doi:10.1152/ajprenal.00396.2002
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Submitted on November 6, 2002
Accepted on March 11, 2003

Bi-directional Regulation of Renal Hemodynamics by Activation of Proteinase-Activated Receptors(PAR) 1 and 2 in the Isolated Perfused Rat Kidney

Yu Gui1, Rodger Loutzenhiser1, and Morley D. Hollenberg2*

1 Department of Pharmacology and Therapeutics, University of Calgary, Calgary, Alberta, Canada
2 Department of Pharmacology and Therapeutics, University of Calgary, Calgary, Alberta, Canada; Department of Medicine, University of Calgary, Calgary, Alberta, Canada

* To whom correspondence should be addressed. E-mail: mhollenb{at}ucalgary.ca.

Proteinase-activated receptors (PARs) are activated by either serine proteinases or synthetic peptides corresponding to the N-terminal tethered ligand sequences that are unmasked by proteolytic cleavage. Although PARs are highly expressed in the kidney, their roles in regulating renal function are not known. In the present study, we evaluated the impact of PAR activation on renal hemodynamics using PAR1- and PAR2-activating peptides (TFLLR-NH2 and SLIGRL-NH2)and proteinases (thrombin and trypsin) as PAR agonists in the isolated perfused rat kidney preparation. PAR1 activation resulted in renal vasoconstriction and a marked reduction in the glomerular filtration rate (GFR). In contrast, PAR2 activation caused vasodilation, partially reversing the vasoconstriction induced by TFLLR-NH2 and angiotensin II (Ang II), and increasing GFR that had been pre-reduced by Ang II. The vasoconstrictor actions of PAR1 activation were abolished by protein kinase C inhibition. The PAR2-induced vasodilation was only partially blocked by L-NAME, suggesting both NO-dependent and -independent mechanisms. Although PAR4 mRNA was detected in renal parenchyma, the PAR4-activating peptide, AYPGKF-NH2, had no effect on RPF. We conclude that PAR2 and PAR2 play bi-directional roles in the regulation of renal hemodynamics.




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