Dietary myo-inositol restores diabetic renal arteriolar reactivity to angiotensin II but not to norepinephrine.
OBJECTIVE
This study addresses the hypothesis that the diminished constriction of renal arterioles to angiotensin II (Ang II) and norepinephrine (NE) in diabetic rats is due to elevated activity in the polyol pathway. This activity results in reduced incorporation of myo-inositol into membrane phospholipids and impaired signal transduction.


METHODS
The left ureter of female Wistar rats (140-160 g) was surgically ligated. Four to six weeks later, streptozotocin (50 mg/kg, i.p.) was injected in half of the rats in induce diabetes. Beginning on the day of streptozotocin injection, diabetic and nondiabetic rats were fed either a standard diet or a diet enriched with 1% myo-inositol. Seven to 10 days later, all rats were anesthetized and the hydronephrotic kidney was bisected and exteriorized in a bath for direct visualization of the renal microvasculature. The constrictor responses of interlobular, afferent, and efferent arterioles to Ang II or NE (applied to the bath) were directly quantitated by in vivo microscopy.


RESULTS
Among diabetic rats, the myo-inositol-enriched diet significantly enhanced the constriction of interlobular, afferent, and efferent arterioles in response to Ang II, so that the responses to the peptide were almost completely restored to normal. Constriction to NE by interlobular arteries and afferent arterioles (but not efferent arterioles) was also significantly attenuated among diabetic rats fed the standard diet. However, unlike what was observed for Ang II, the myo-inositol-enriched diet did not enhance constriction to NE among diabetic rats.


CONCLUSIONS
These data indicate that different mechanisms are responsible for decreased renal arteriolar constriction due to Ang II and NE in early diabetes. Diminished arteriolar constriction due to Ang II, but not to NE, may be linked to altered myo-inositol metabolism.
Inman
S R
SR
Department of Physiology & Biophysics School of Medicine, University of Louisville, Kentucky, USA.
Porter
J P
JP
Fleming
J T
JT
D000109:Acetylcholine / Q000494:pharmacology; D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D001160:Arterioles / Q000187:drug effects*; D001786:Blood Glucose / Q000032:analysis; D003921:Diabetes Mellitus, Experimental / Q000178:diet therapy / Q000503:physiopathology; D003928:Diabetic Nephropathies / Q000178:diet therapy* / Q000503:physiopathology; D004040:Dietary Carbohydrates / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D006869:Hydronephrosis / Q000503:physiopathology*; D007294:Inositol / Q000008:administration & dosage / Q000494:pharmacology*; D007668:Kidney / Q000098:blood supply* / Q000378:metabolism; D008563:Membrane Lipids / Q000378:metabolism*; D008833:Microcirculation / Q000187:drug effects; D009638:Norepinephrine / Q000494:pharmacology*; D010743:Phospholipids / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D012083:Renin / Q000097:blood; D013311:Streptozocin; D014661:Vasoconstriction / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000008:administration & dosage / Q000494:pharmacology*
D001786:Blood Glucose; D004040:Dietary Carbohydrates; D008563:Membrane Lipids; D010743:Phospholipids; D014662:Vasoconstrictor Agents; D000804:Angiotensin II; D007294:Inositol; D013311:Streptozocin; D012083:Renin; D000109:Acetylcholine; D009638:Norepinephrine