Document Detail


Effects of indomethacin on responses of regional kidney perfusion to vasoactive agents in rabbits.
MedLine Citation:
PMID:  12207565     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
1. To determine whether differential release of products of arachidonic acid metabolism, via the cyclo-oxygenase pathway, underlies the diversity of responses of regional kidney perfusion to vasoactive agents, we tested the effects of intravenous indomethacin on responses to renal arterial bolus doses of vasoactive agents in pentobarbitone-anaesthetized rabbits. 2. Total renal blood flow (RBF) and regional kidney perfusion were determined by transit time ultrasound flowmetry and laser-Doppler flowmetry, respectively. 3. Responses of regional kidney blood flow to vasoactive agents were diverse: noradrenaline reduced cortical but not medullary perfusion, [Phe 2,Ile 3,Orn 8]-vasopressin reduced medullary perfusion more than cortical perfusion, endothelin-1 and angiotensin II increased medullary perfusion in the face of reduced cortical perfusion, while acetylcholine, bradykinin and the nitric oxide donor methylamine hexamethylene methylamine (MAHMA) NONOate all increased both cortical and medullary perfusion. 4. Indomethacin administration was followed by reductions in total RBF (17 +/- 6%), cortical perfusion (13 +/- 5%) and medullary perfusion (40 +/- 8%). Angiotensin II- and endothelin-1-induced increases in medullary perfusion were abolished by indomethacin, but indomethacin had no significant effects on responses of regional kidney perfusion to acetylcholine, bradykinin, MAHMA NONOate, noradrenaline and [Phe 2,Ile 3,Orn 8]-vasopressin. 5. Our results suggest that vasodilator cyclo-oxygenase products contribute to the maintenance of resting renal vascular tone, particularly in vascular elements controlling medullary perfusion. Cyclo-oxygenase products also appear to mediate endothelin-1- and angiotensin II-induced increases in medullary perfusion. However, regionally specific engagement of cyclo-oxygenase-dependent arachidonic acid metabolism does not appear to contribute to the differential effects of noradrenaline and [Phe 2,Ile 3,Orn 8]-vasopressin on cortical and medullary perfusion.
Authors:
Jeremy J Oliver; Niwanthi W Rajapakse; Roger G Evans
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Clinical and experimental pharmacology & physiology     Volume:  29     ISSN:  0305-1870     ISO Abbreviation:  Clin. Exp. Pharmacol. Physiol.     Publication Date:  2002 Oct 
Date Detail:
Created Date:  2002-09-04     Completed Date:  2003-03-03     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0425076     Medline TA:  Clin Exp Pharmacol Physiol     Country:  Australia    
Other Details:
Languages:  eng     Pagination:  873-9     Citation Subset:  IM    
Affiliation:
Department of Physiology, Monash University, Melbourne, Victoria, Australia.
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MeSH Terms
Descriptor/Qualifier:
Animals
Cyclooxygenase Inhibitors / pharmacology
Indomethacin / pharmacology*
Infusions, Intravenous
Injections, Intra-Arterial
Kidney / blood supply,  drug effects*,  enzymology
Male
Prostaglandin-Endoperoxide Synthases / metabolism
Rabbits
Renal Circulation / drug effects*,  physiology
Vasoconstrictor Agents / pharmacology*
Chemical
Reg. No./Substance:
0/Cyclooxygenase Inhibitors; 0/Vasoconstrictor Agents; 53-86-1/Indomethacin; EC 1.14.99.1/Prostaglandin-Endoperoxide Synthases

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