Biophysical signals underlying myogenic responses in rat interlobular artery

Abstract

To assess cellular mechanisms mediating myogenic responses of interlobular artery (ILA), experiments were performed with the use of isolated perfused hydronephrotic kidneys. ILAs were divided into 3 groups according to their basal diameters: proximal (>60 μm), intermediate (40 to 60 μm), and distal (<40 μm) ILAs. Myogenic responses were obtained by stepwise increase in perfusion pressure. Greater myogenic responsiveness was observed in ILAs with smaller diameters. Diltiazem (10 μmol/L) inhibited myogenic responses of all segments of ILAs. Furthermore, gadolinium (10 μmol/L), a mechanosensitive cation channel blocker, abolished myogenic responses of distal but not proximal ILA. In contrast, 2-nitro-4- carboxphenyl-N, N-diphenyl-carbamate (200 μmol/L), an inhibitor of phospholipase C, prevented myogenic responses of proximal but not distal ILA. Finally, basal proximal ILA diameters were increased by treatment with 50 nmol/L of staurosporine (P<0.05), and subsequent addition of thapsigargin (1 μmol/L) blocked myogenic contraction of proximal ILAs. Myogenic responses of intermediate ILAs exhibited characteristics between those of distal and proximal ILAs. Our data indicate that underlying mechanisms for myogenic responses differ in distinct segments of ILAs. The present results suggest that mechanosensitive cation channels are involved in myogenic constriction of distal ILAs. Finally, our findings provide evidence that the stimulation of phospholipase C mediates myogenic contraction of proximal ILAs.