Adult sympathetic and vascular dysfunction in experimental juvenile-onset diabetes mellitus.
This study was designed to determine if vascular dysfunction and enhanced norepinephrine sensitivity occurring in early experimental juvenile diabetes (S. M. Mueller, T. M. Mueller, and P. J. Ertel, 1982, Amer. J. Physiol. 243, H139-H144) persist, improve, or worsen in adulthood. Alloxan was administered to rats at 4 weeks of age and they were studied 14 weeks later. After Seconal anesthesia, the hindquarters of diabetic and control rats were perfused at a constant flow rate per 100 g through the abdominal aorta with oxygenated Tyrode solution containing dextran. Efflux was from the ligated and severed inferior vena cava. In order to test the effect of a strong sympathetic stimulus producing reflex peripheral vasoconstriction, the cephalad portions of the rats were rapidly hemorrhaged. The time to the maximal increase was significantly longer in the diabetics (122 +/- 6 sec, P less than 0.05) than in the controls (102 +/- 5 sec) and the increase in perfusion pressure was markedly less in the diabetics (D) (48 +/- 9 mm Hg, P less than 0.01) than in the age-matched controls (C) (88 +/- 10 mm Hg). The threshold to norepinephrine in the perfusate was determined. The threshold was significantly lower in D than in age-matched C [0.112 +/- 0.026 (P less than 0.05) vs 0.265 +/- 0.057 micrograms/ml, respectively]. The maximum vasoconstrictor capacity of the vasculature was tested with supramaximal doses of vasopressin and was significantly lower in D than in C [190 +/- 10 (P less than 0.001) vs 284 +/- 15 mm Hg, respectively]. These data suggest that both vasculopathy and enhanced norepinephrine sensitivity persist in chronic uncontrolled experimental diabetes mellitus. However, when the severity of the abnormalities was compared to early experimental diabetes mellitus, mild improvement had occurred--an apparent adaptation to the diabetic state as the animal grew.
D000375:Aging; D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D001794:Blood Pressure; D001835:Body Weight; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D005230:Fatty Acids, Nonesterified / Q000097:blood; D006470:Hemorrhage / Q000503:physiopathology; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D014655:Vascular Resistance; D014661:Vasoconstriction; D014664:Vasodilation; D014667:Vasopressins / Q000494:pharmacology
D001786:Blood Glucose; D005230:Fatty Acids, Nonesterified; D014667:Vasopressins; D009638:Norepinephrine