Dopamine attenuates the contractile response to angiotensin II in isolated rat glomeruli and cultured mesangial cells.
Recent evidence suggests that dopamine may alter kidney function by actions not only in the renal vasculature but also at the glomerular-mesangial level. We studied this phenomenon by examining the ability of dopamine to antagonize the contractile properties of angiotensin II in isolated rat glomeruli and cultured mesangial cells. In isolated rat glomeruli angiotensin II caused a decrease in the planar surface area, indicating glomerular contraction, an effect that was abolished by coincubation with dopamine. Angiotensin II also mediated shape changes in cultured mesangial cells, which resulted in a decline in their planar areas. Simultaneous addition of dopamine prevented these decreases in cell size. In mesangial cells grown on a flexible silicone rubber support, angiotensin II addition enhanced wrinkling of the mobile surface. This indicated that the angiotensin-II-induced decrease in cell size observed in cells grown on conventional substrata represented contraction. Conversely, dopamine caused a rapid reduction in wrinkling of the surfaces from control cells as well as those previously treated with angiotensin II, actions consistent with cell relaxation. The prostaglandin inhibitor indomethacin did not alter the ability of dopamine to attenuate angiotensin-II-associated reductions in mesangial cell surface area. Direct determination of mesangial cell prostaglandin-E2 production showed that dopamine did not change either basal synthesis or angiotensin-II-stimulated synthesis of prostaglandin. The results demonstrate that dopamine antagonizes the constrictor effect of angiotensin II at the glomerular-mesangial level. This action of dopamine is prostaglandin independent. These findings support a role for dopamine in the regulation of glomerular filtration and may provide a rationale for its use during states of renal vasoconstriction.
Barnett
R
R
Singhal
P C
PC
Scharschmidt
L A
LA
Schlondorff
D
D
D000804:Angiotensin II / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D000818:Animals; D002478:Cells, Cultured; D015232:Dinoprostone; D004298:Dopamine / Q000494:pharmacology*; D005920:Glomerular Mesangium / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D007213:Indomethacin / Q000494:pharmacology; D007678:Kidney Glomerulus / Q000187:drug effects*; D008297:Male; D011458:Prostaglandins E / Q000096:biosynthesis; D051381:Rats; D011919:Rats, Inbred Strains
D011458:Prostaglandins E; D000804:Angiotensin II; D015232:Dinoprostone; D004298:Dopamine; D007213:Indomethacin