The role of alpha-adrenergic receptors in the vasoconstrictor response induced by indomethacin in the kidney.
The effect of indomethacin, an inhibitor of prostaglandin (PG) synthesis, was studied on the renal circulation, Na+ and water excretion in anaesthesized dogs during alpha-receptor inhibition. Indomethacin decreased cortical blood flow (CBFcontr, 454 +/- 142; CBFindo, 332 +/- 51 ml per min per 100 g; p less than 0.02) as well as medullary blood flow (OMBFcontr, 339 +/- 95; OMBFindo, 183 +/- 46 ml per min per 100 g; p less than 0.001), salt and water excretion, further it caused a shift in the intrarenal blood flow distribution toward the cortex. Alpha-blockade prevented the indomethacin-induced vasoconstriction in the cortex (CBF alpha inhibition + indo, 455 +/- 76 ml per min per 100 g) but not in the medullar (OMBF alpha inhibition + indo, 259 +/- 102 ml per min per 100 g, p less than 0.05). Alpha-blockade failed to prevent the indomethacin-induced antidiuresis, antinatriuresis and the intrarenal blood flow redistribution. GFR remained unaffected in all three series of studies. Our experimental findings are in line with the presumption that alpha-receptors are involved in the renal circulatory changes caused by indomethacin, probably as a result of an enhanced NE release during the inhibition of PG production. A NE--PG feed back mechanism is suggested in the regulation of renal circulation. The reduction of salt and water output induced by indomethacin appears to be independent of the alterations in renal haemodynamics, and seems rather to be the result of enhanced Na+ reabsorption, predominantly at the distal segment of the nephron, in the absence of PG, and/or a direct action of indomethacin.
D000818:Animals; D004231:Diuresis / Q000187:drug effects; D004285:Dogs; D005260:Female; D007213:Indomethacin / Q000494:pharmacology*; D007668:Kidney / Q000098:blood supply*; D007671:Kidney Concentrating Ability / Q000187:drug effects; D007672:Kidney Cortex / Q000098:blood supply*; D007679:Kidney Medulla / Q000098:blood supply; D008297:Male; D009318:Natriuresis / Q000187:drug effects; D011941:Receptors, Adrenergic / Q000502:physiology*; D011942:Receptors, Adrenergic, alpha / Q000502:physiology*; D013268:Stimulation, Chemical; D014661:Vasoconstriction / Q000187:drug effects*; D014662:Vasoconstrictor Agents
D011941:Receptors, Adrenergic; D011942:Receptors, Adrenergic, alpha; D014662:Vasoconstrictor Agents; D007213:Indomethacin