| For the first time, the microcirculation of the kidney among diabetic rats was directly studied. By direct visualization of multiple microvascular sites it was possible to address the following concepts: (1) diminished reactivity to a specific constrictor hormone may occur at select, but not all, microvascular sites, (2) a specific microvascular site may exhibit a diminished reactivity to select, but not all, constrictor hormones, (3) endogenous prostaglandins may contribute to the decreased renal microvascular reactivity to vasoconstrictor hormones, and (4) depletion of intracellular myo-inositol is the common mechanism for diminished microvascular reactivity to multiple constrictors. To address these concepts the rat hydronephrotic kidney preparation was used since it allows for direct visualization of preglomerular and postglomerular sites.;The results reveal that diabetic afferent and efferent arterioles exhibited a diminished constrictor response to angiotensin II. The angiotensin II responses for the interlobular arteries among diabetic rats also tended to be blunted. The preglomerular vessels among diabetic rats were hyporesponsive to norepinephrine and the alpha-1 agonist, phenylephrine. Specifically, the interlobular arteries were hyporesponsive to norepinephrine and the afferent arterioles were hyporesponsive to phenylephrine. Pre- and post-glomerular vessels among diabetic rats constricted to the same percent from baseline diameter to the alpha-2 agonist, UK 14304, as the non-diabetic rats at all kidney bath concentrations.;Inhibition of renal prostaglandin synthesis enhanced the constrictor response to angiotensin II among the diabetic afferent and efferent arterioles and normalized the constrictor response of the diabetic interlobular arteries. Dietary myo-inositol supplementation normalized the pre- and postglomerular response to angiotensin II, but not to norepinephrine, among the diabetic rats.;These results suggest that an increased synthesis of endogenous renal vasodilator prostaglandins is attenuating the constrictor response to angiotensin II among the interlobular arteries of diabetic rats and contributes to, but is not solely responsible for, the hyporeactivity to angiotensin II among the afferent and efferent arterioles. The diminished constrictor response to angiotensin II, and possibly phenylephrine, appears to be due to the depletion of vascular smooth muscle inositol pools. These myo-inositol pools are essential for angiotensin II and alpha-1 agonist-mediated vascular smooth muscle constriction. The mechanism allowing for the diminished renal microvascular reactivity to norepinephrine remains unresolved.;A major concept that has evolved from this study is that microvascular alterations are not uniformly the same among all diabetic vascular beds, but are tissue specific. Future treatment modalities for diabetic patients must take this into consideration. |
