Interaction between thromboxane A2 and angiotensin II in postischemic renal vasoconstriction in dogs.
The kidney responds to periods of ischemia with vasoconstriction and a decrease in glomerular filtration rate (GFR) on reperfusion. The mediators of this response have not been fully identified. In this study, we examined the contribution of angiotensin II (AII), thromboxane A2 (TXA2) and the interaction between them to this response. Anesthetized dogs were subjected to 30 min of clamping of both renal arteries. Renal hemodynamics and function were followed from 60 min before and for 105 min after clamping. Dogs were divided into salt-depleted (AII-stimulated) and captopril-treated (AII-inhibited) groups. Each group included dogs that received either the TXA2 synthase inhibitor CGS 13080 or its vehicle (controls) starting 30 min before renal artery clamping and lasting to the end of the experiment. In captopril-treated control dogs, 30 min of ischemia induced a 25% fall in renal blood flow (RBF). GFR initially fell by 75%, but recovered to 64% of base-line value 60 to 90 min after release of the clamp. In captopril-treated dogs, CGS 13080 prevented the fall in RBF, but the GFR response was similar to vehicle-treated dogs. In control dogs, both GFR and RBF responses were enhanced in salt-depleted compared with captopril-treated dogs; the decrease in RBF (44%) was greater, and the recovery in GFR, which fell by 89%, less. In salt-depleted, CGS 13080-treated dogs, the 30% fall in RBF was less than its control, but greater than dogs treated with captopril and CGS 13080. The change in GFR was similar to the other groups.(ABSTRACT TRUNCATED AT 250 WORDS)
Abels
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BC
Department of Surgery, Vanderbilt University School of Medicine, Nashville, Tennessee.
Branch
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RA
Sabra
R
R
D000804:Angiotensin II / Q000502:physiology*; D000818:Animals; D002216:Captopril / Q000494:pharmacology; D004285:Dogs; D005919:Glomerular Filtration Rate / Q000187:drug effects; D007093:Imidazoles / Q000494:pharmacology; D007511:Ischemia / Q000503:physiopathology*; D007668:Kidney / Q000098:blood supply*; D011725:Pyridines / Q000494:pharmacology; D012079:Renal Circulation / Q000187:drug effects; D013928:Thromboxane A2 / Q000502:physiology*; D014661:Vasoconstriction / Q000187:drug effects*
D007093:Imidazoles; D011725:Pyridines; D000804:Angiotensin II; D013928:Thromboxane A2; D002216:Captopril; C037787:pirmagrel