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Renal medullary interstitial infusion is a flawed technique for examining vasodilator mechanisms in anesthetized rabbits.
J Pharmacol Toxicol Methods. 2002 May-Jun; 47(3):153-9.JP

Abstract

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.

Authors+Show Affiliations

Department of Physiology, Monash University, P.O. Box 13F, Victoria 3800, Australia.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

12628306

Citation

Kalyan, Aparna, et al. "Renal Medullary Interstitial Infusion Is a Flawed Technique for Examining Vasodilator Mechanisms in Anesthetized Rabbits." Journal of Pharmacological and Toxicological Methods, vol. 47, no. 3, 2002, pp. 153-9.
Kalyan A, Eppel GA, Anderson WP, et al. Renal medullary interstitial infusion is a flawed technique for examining vasodilator mechanisms in anesthetized rabbits. J Pharmacol Toxicol Methods. 2002;47(3):153-9.
Kalyan, A., Eppel, G. A., Anderson, W. P., Oliver, J. J., & Evans, R. G. (2002). Renal medullary interstitial infusion is a flawed technique for examining vasodilator mechanisms in anesthetized rabbits. Journal of Pharmacological and Toxicological Methods, 47(3), 153-9.
Kalyan A, et al. Renal Medullary Interstitial Infusion Is a Flawed Technique for Examining Vasodilator Mechanisms in Anesthetized Rabbits. J Pharmacol Toxicol Methods. 2002 May-Jun;47(3):153-9. PubMed PMID: 12628306.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Renal medullary interstitial infusion is a flawed technique for examining vasodilator mechanisms in anesthetized rabbits. AU - Kalyan,Aparna, AU - Eppel,Gabriela A, AU - Anderson,Warwick P, AU - Oliver,Jeremy J, AU - Evans,Roger G, PY - 2003/3/12/pubmed PY - 2003/10/2/medline PY - 2003/3/12/entrez SP - 153 EP - 9 JF - Journal of pharmacological and toxicological methods JO - J Pharmacol Toxicol Methods VL - 47 IS - 3 N2 - 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. SN - 1056-8719 UR - https://www.unboundmedicine.com/medline/citation/12628306/Renal_medullary_interstitial_infusion_is_a_flawed_technique_for_examining_vasodilator_mechanisms_in_anesthetized_rabbits_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1056-8719(02)00230-7 DB - PRIME DP - Unbound Medicine ER -