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Renal medullary interstitial infusion is a flawed technique for examining vasodilator mechanisms in anesthetized
Aparna Kalyan1, Gabriela A Eppel, Warwick P Anderson
1Department of Physiology, Monash University, P.O. Box 13F, Victoria 3800, Australia.
Introduction:
In rats, medullary interstitial (IMI) infusion is a useful technique for selective delivery of pharmacological agents to the renal medulla, in both acute and chronic experimental settings. We examined the feasibility of using this technique for delivery of vasodilators in rabbits, since this larger species would provide a number of advantages, particularly in long-term studies of circulatory control.
Methods:
Rabbits were anesthetized with pentobarbitone and artificially ventilated. Catheters were placed in a side branch of the renal artery and/or the renal medullary interstitium. Renal blood flow (RBF) was determined by transit-time ultrasound flowmetry, and blood flow in the cortex and medulla was estimated by laser Doppler flowmetry.
Results:
Pilot studies showed that renal arterial (IRA) infusions of bradykinin (10-300 ng/kg/min) and adenosine (1-10 ng/kg/min) produced only transient renal vasodilatation. IRA infusions of methylamine hexamethylene methylamine (MAHMA) NONOate (100-1000 ng/kg/min) and acetylcholine (10-250 ng/kg/min) produced dose-dependent and sustained increases in RBF and reductions in arterial pressure at the highest doses. However, IMI infusion of the same doses did not consistently increase medullary laser Doppler flux (MLDF). After IRA MAHMA NONOate and IMI acetylcholine, RBF fell to below its resting level. IRA boluses of acetylcholine (10-1250 ng/kg), bradykinin (2-250 ng/kg), and MAHMA NONOate (100-3000 ng/kg) dose-dependently increased RBF and CLDF and MLDF.
Discussion:
We had previously validated the IMI infusion technique for intramedullary delivery of vasoconstrictors in rabbits. Our present results indicate that this technique has limited application for delivery of vasodilator agents, in part because counterregulatory vasoconstrictor mechanisms are activated.
Insights
Medullary interstitial infusion in rabbits is not ideal for delivering vasodilators due to counterregulatory vasoconstriction. This technique is better suited for vasoconstrictor delivery in renal studies.
Area of Science:
- Nephrology
- Pharmacology
- Physiology
Background:
- Medullary interstitial (IMI) infusion is established for selective renal medulla drug delivery in rats.
- Larger species like rabbits offer advantages for long-term circulatory control studies.
Purpose of the Study:
- To assess the feasibility of IMI infusion for delivering vasodilators in rabbits.
- To compare IMI and renal arterial infusion of vasodilators in rabbits.
Main Methods:
- Rabbits underwent anesthesia and artificial ventilation.
- Catheters were placed in the renal artery and/or medullary interstitium.
- Renal blood flow (RBF) was measured using ultrasound flowmetry; cortical and medullary blood flow were assessed via laser Doppler flowmetry.
Main Results:
- Renal arterial infusions of acetylcholine and MAHMA NONOate increased RBF dose-dependently.
- Medullary interstitial infusions of these agents did not consistently increase medullary blood flow.
- Both renal arterial and medullary interstitial infusions sometimes led to a subsequent drop in RBF.
Conclusions:
- The IMI infusion technique has limited utility for delivering vasodilators in rabbits.
- Counterregulatory vasoconstrictor mechanisms appear to be activated, hindering vasodilator efficacy via IMI.