The role of intrarenal prostaglandins and angiotensin II in acute cyclosporine-induced vasoconstriction.
Cyclosporine causes intrarenal vasoconstriction, which may account for its nephrotoxic effects. In this study we investigated the role of endogenous prostaglandins and angiotensin II in cyclosporine-induced intrarenal vasoconstriction. Split hydronephrotic kidneys in decerebrate rats (n = 16) were suspended in an environmentally controlled tissue bath. Interlobular, afferent, and efferent arteriolar diameters and red blood cell velocity were measured by in vivo video-microscopy and Doppler velocimetry. After topical application of cyclosporine to the kidney in the tissue bath, a 12% +/- 2% constriction of the interlobular and a 28% +/- 5% reduction in interlobular blood flow occurred. The afferent and efferent arterioles also constricted by 13% +/- 2% and 10% +/- 3%, respectively. Prostaglandin inhibition with mefenemate augmented this vasoconstriction (16% +/- 2% at interlobular and 21% +/- 4% at afferent arterioles) and reduction in interlobular blood flow (38% +/- 8%) below baseline values. Mefenemate alone resulted in a 35% +/- 5% reduction in interlobular blood flow, which was not further augmented by cyclosporine. In contrast, local competitive angiotensin II-receptor inhibition with saralasin maintained blood flow after cyclosporine and prevented intrarenal vasoconstriction by cyclosporine. This suggests that prostaglandins protect against intrarenal vasoconstriction and that acute cyclosporine-induced vasoconstriction is mediated through angiotensin II receptors.
Abraham
J S
JS
Department of Surgery, University of Louisville School of Medicine, KY 40292.
Bentley
F R
FR
Garrison
R N
RN
D015059:1-Sarcosine-8-Isoleucine Angiotensin II / Q000494:pharmacology; D000804:Angiotensin II / Q000502:physiology*; D000818:Animals; D001783:Blood Flow Velocity / Q000187:drug effects; D003524:Cyclosporins / Q000494:pharmacology*; D006439:Hemodynamics / Q000187:drug effects; D007668:Kidney / Q000098:blood supply*; D008297:Male; D008528:Mefenamic Acid / Q000494:pharmacology; D008833:Microcirculation / Q000187:drug effects; D011453:Prostaglandins / Q000502:physiology*; D051381:Rats; D011919:Rats, Inbred Strains; D011945:Receptors, Angiotensin / Q000187:drug effects; D013997:Time Factors; D014661:Vasoconstriction / Q000187:drug effects*
D003524:Cyclosporins; D011453:Prostaglandins; D011945:Receptors, Angiotensin; D000804:Angiotensin II; D008528:Mefenamic Acid; D015059:1-Sarcosine-8-Isoleucine Angiotensin II