ABSTRACT
We examined endothelium-dependent and -independent hyperpolarizations and endothelium-dependent relaxation responses in carotid arteries isolated from streptozotocin-induced diabetic rats and age-matched controls. The resting membrane potentials were not significantly different between control and diabetic carotid arteries. The endothelium-dependent hyperpolarization induced by acetylcholine, which was inhibited by TEA but not by glibenclamide or by treatment with either a high concentration of glucose or pertussis toxin, was significantly weaker in diabetic arteries than in the controls. The relaxation responses to acetylcholine in carotid artery rings were significantly decreased in streptozotocin-diabetic rats. Treatment with NG-nitro-L-arginine (L-NOARG) inhibited the acetylcholine-induced maximal relaxation by 80% and 30% in control and streptozotocin-diabetic rats, respectively, and the simultaneous application of L-NOARG and indomethacin had a more potent inhibitory effect on this relaxation in both groups. The release of 6-keto-prostaglandin F1alpha and that of thromboxane A2 in response to methoxamine or methoxamine plus acetylcholine were both markedly decreased in diabetic rats. The cromakalim-induced hyperpolarization of the carotid artery, which was completely prevented by glibenclamide, was also significantly weaker in diabetic arteries than in the controls. These results suggest that changes in (1) various K+ channels on smooth muscle, (2) the biosynthesis of cyclooxygenase products and (3) endothelium-dependent relaxation may be important factors in the development of diabetic complications in the carotid artery.
Subject(s)
Carotid Arteries/physiology , Diabetes Mellitus, Experimental/physiopathology , Endothelium, Vascular/physiology , Muscle, Smooth, Vascular/physiology , 6-Ketoprostaglandin F1 alpha/pharmacology , Acetylcholine/pharmacology , Animals , Carotid Arteries/drug effects , Cromakalim/pharmacology , In Vitro Techniques , Isometric Contraction/drug effects , Male , Membrane Potentials/drug effects , Microelectrodes , Muscle Relaxation/drug effects , Muscle, Smooth, Vascular/drug effects , Pertussis Toxin , Rats , Rats, Wistar , Thromboxane B2/pharmacology , Virulence Factors, Bordetella/pharmacologyABSTRACT
The purpose of this study was to study changes in the sympathetic nerves of the vas deferens in 10-week-old streptozotocin-induced diabetic rats. To assess the activity of autonomic neurons, we recorded the amplitude and frequency of spontaneous junction potentials in vasa deferentia from age-matched controls and streptozotocin-induced diabetic rats. No change in the resting membrane potential of the smooth muscle of the vas deferens was found in streptozotocin-induced diabetic rats. The frequency of spontaneous junction potentials was significantly increased in the streptozotocin-induced diabetic rats and their amplitude was also markedly increased. The dose-response curve for the contractile response of the vas deferens to noradrenaline was significantly shifted to the right and the apparent affinity (pD2 value) was significantly decreased in streptozotocin-induced diabetic rats. These results suggest that degeneration of sympathetic neurons may occur in the vas deferens of 10-week streptozotocin-induced diabetic rats and that the greater amplitude of the spontaneous junction potentials may be related to an increase in Ca2+ mobilization, though the increase in Ca2+ mobilization does not lead to an enhanced contractile response.
