Effects of streptozotocin-diabetes on sympathetic nerve, endothelial and smooth muscle function in the rat mesenteric arterial bed.
Mesenteric arterial function was assessed in constantly perfused preparations isolated from rats 12 weeks after treatment with streptozotocin (65 mg kg-1, i.p.) to induce diabetes. Frequency-dependent vasoconstrictor responses to electrical field stimulation of sympathetic nerves (4-32 Hz, 0.1 ms, 90V, 30 s) were severely attenuated in preparations from streptozotocin-diabetic rats, although dose-dependent vasoconstrictions to the sympathetic cotransmitters noradrenaline and ATP, as well as to potassium chloride, were not significantly changed. Dose-dependent relaxations to the endothelium-dependent vasodilators acetylcholine and ATP were significantly impaired in preparations from streptozotocin-diabetic rats, although endothelium-independent vasodilatation to sodium nitroprusside was unimpaired. These results suggest 12 weeks after induction of streptozotocin-diabetes in rats there is pre-junctional impairment of sympathetic neurotransmission and impaired endothelial function of the mesenteric arteries. This is in contrast to our previous findings that at 8 weeks after induction of streptozotocin-diabetes sympathetic nerve and endothelial function is normal, although sensory-motor vasodilatation is severely attenuated. It is suggested that selective changes occur in mesenteric arterial function after streptozotocin treatment depending on the duration of diabetes; sensory-motor nerves are affected first, followed by sympathetic nerves and the endothelium, while the smooth muscle is relatively resistant to change.
Ralevic
V
V
Department of Anatomy and Developmental Biology, University College London, UK.
Belai
A
A
Burnstock
G
G
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D004730:Endothelium, Vascular / Q000503:physiopathology*; D066298:In Vitro Techniques; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000503:physiopathology*; D051381:Rats; D017208:Rats, Wistar; D013311:Streptozocin; D013564:Sympathetic Nervous System / Q000503:physiopathology*; D014661:Vasoconstriction / Q000187:drug effects
D013311:Streptozocin; D000109:Acetylcholine