Intra- and extrarenal arteries exhibit different profiles of contractile responses in high glucose conditions.
OBJECTIVE
The renal artery (RA) has been extensively investigated for the assessment of renal vascular function/dysfunction; however, few studies have focused on the intrarenal vasculature.


METHODS
We devised a microvascular force measurement system, which allowed us to measure contractions of interlobar arteries (ILA), isolated from within the mouse kidney and prepared without endothelium.


RESULTS
KCl (50 mM) induced similar force development in the aorta and RA but responses in the ILA were about 50% lower. Treatment of RA with 10 microM phenylephrine (PE), 10 nM U46619 (thromboxane A(2) analogue) or 10 microM prostaglandin F(2 alpha) elicited a response greater than 150% of that induced by KCl. In ILA, 10 nM U46619 elicited a response that was 130% of the KCl-induced response; however, other agonists induced levels similar to that induced by KCl. High glucose conditions (22.2 mM glucose) significantly enhanced responses in RA and ILA to PE or U46619 stimulation. This enhancement was suppressed by rottlerin, a calcium-independent PKC inhibitor, indicating that glucose-dependent, enhanced small vessel contractility in the kidney was linked to the activation of calcium-independent PKC.


CONCLUSIONS
Extra- and intrarenal arteries exhibit different profiles of agonist-induced contractions. In ILA, only U46619 enhanced small vessel contractility in the kidney, which might lead to renal dysfunction and nephropathy through reduced intrarenal blood flow rate. A model has been established, which will allow the assessment of contractile responses of intrarenal arteries from murine models of renal disease, including type 2 diabetes.
Nobe
K
K
Department of Pharmacology, School of Pharmaceutical Sciences, SHOWA University, Tokyo, Japan. kojinobe@pharm.showa-u.ac.jp
Nezu
Y
Y
Tsumita
N
N
Hashimoto
T
T
Honda
K
K
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / Q000494:pharmacology; D000818:Animals; D015237:Dinoprost / Q000494:pharmacology; D005947:Glucose / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D009119:Muscle Contraction; D010656:Phenylephrine / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D012077:Renal Artery / Q000187:drug effects* / Q000502:physiology
D047428:Protein Kinase Inhibitors; D010656:Phenylephrine; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D015237:Dinoprost; D011493:Protein Kinase C; D005947:Glucose