Effects of streptozotocin-induced hyperglycemia on agonist-stimulated phosphatidylinositol turnover in rat aorta.
Altered vascular sensitivity and responsiveness has been previously described in various stages of experimental diabetes mellitus. Increases in membrane bound Ca2+ and intracellular calcium in diabetic aorta have been postulated to explain excitation-coupling dysfunction in diabetic vascular smooth muscle (VSM). Receptor-mediated phosphatidylinositol (PI) hydrolysis is known to activate VSM contraction; thus contractile changes in diabetic aorta could be functionally linked to abnormal PI turnover. To evaluate this possibility, parallel experiments were undertaken to study contractility and receptor-stimulated PI turnover with norepinephrine (NE), phenylephrine (PE), and serotonin (5-HT). At 7 and 28 days following injection of streptozotocin with production of the hyperglycemic state, aortas were harvested for contractile and PI turnover experiments. No differences in the contractile cumulative dose responses or receptor-mediated PI turnover were measured in the 7 day group. At 28 days, vascular supersensitivity and increased responsiveness were observed. PI hydrolysis in basal and agonist-stimulated aorta was, however, markedly decreased at 28 days. These findings suggest that mobilization and utilization of Ca2+ during contraction occur independently of receptor-stimulated PI hydrolysis in aorta from hyperglycemic rats. The duration of hyperglycemia also significantly effects contractility and PI turnover in rat aorta.
Legan
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Department of Internal Medicine, Texas Tech University Health Sciences Center, Lubbock 79430.
D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D006943:Hyperglycemia / Q000139:chemically induced / Q000378:metabolism*; D066298:In Vitro Techniques; D007294:Inositol / Q000378:metabolism; D007295:Inositol Phosphates / Q000096:biosynthesis* / Q000302:isolation & purification; D008297:Male; D009119:Muscle Contraction; D009130:Muscle, Smooth / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D009638:Norepinephrine / Q000494:pharmacology*; D010656:Phenylephrine / Q000494:pharmacology*; D010716:Phosphatidylinositols / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D012016:Reference Values; D012701:Serotonin / Q000494:pharmacology*; D013311:Streptozocin; D013403:Sugar Phosphates / Q000096:biosynthesis*
D001786:Blood Glucose; D007295:Inositol Phosphates; D010716:Phosphatidylinositols; D013403:Sugar Phosphates; D010656:Phenylephrine; D012701:Serotonin; D007294:Inositol; D013311:Streptozocin; D009638:Norepinephrine