Elevated renal perfusion pressure (RPP) elicits constriction of renal afferent arterioles (AFF), which comprises two mechanisms, myogenic response and tubuloglomerular feedback (TGF). This study examined whether pressure-induced AFF constriction was impaired in acute and chronic hyperglycemia. Intravital CCD camera was used to visualize the renal microcirculation. In normoglycemic rats, elevated RPP caused 17.5±2.0% AFF constriction. Acute hyperglycemia by infusion of high glucose solution elicited AFF vasodilation, and blunted the pressure-induced constriction(一8.7±1.0%). In contrast, the same elevation in plasma osmolality with mannitol failed to alter the basal diameter or the pressure-induced constriction of AFF. In acute hyperglycemic rats, both gadolinium (a myogenic response inhibitor)and furosemide la TGF inhibitor) inhibited the pressure-induced AFF constriction. During the inhibition of myogenic tone by gadolinium, the inhibition of nNOS by S-methyl-L-thiocitrulline (L-SMTC) restored the acute hyperglycemis-induced impaired AFF constriction, but this ameliorating action was absentduring the TGF inhibition by furosemide, suggesting selective activity of nNOS-associated NO on TGF. Similarly, in chronic hyperglycemic (Zucker obese) rats, myogenic response and TGF were blunted, and L-SMTC ameliorated the blunted TGF response. In conclusion, hyperglycemia causes impaired pressure response in both acute and chronic hyperglycemia. The blunted response is attributed to impairment in myogenic and TGF-mediated AFF constriction; the latter effect is caused by enhanced activity of nNOS.

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