Summary
The effect of STZ-induced diabetes of 8-weeks duration was examined on nitric oxide-mediated neurotransmission in the rat anococcygeus muscle. In the presence of noradrenergic blockade and raised tissue tone, relaxant responses to nerve stimulation (0.5–5 Hz, for 10 s), sodium nitroprusside (5 and 10 nmol/l) and nitric oxide (1 and 3 μmol/l) were significantly reduced in anococcygeus muscles from diabetic rats compared to responses from control rats (p <0.05). In contrast, relaxations to papaverine (3 and 10 μmol/l were not reduced in tissues from diabetic rats. The nitric oxide synthesis inhibitor NOLA (100 μmol/l) abolished relaxant responses to nerve stimulation but had no effect on responses to any of the relaxant agents used. Exposure to NOLA at 10 μmol/l reduced stimulation-induced relaxations; this reduction was significantly greater in tissues from the diabetic group than from the control group (p <0.05), probably as a consequence of the smaller relaxant responses in muscles from diabetic rats. Contractile responses to nerve stimulation (1–10 Hz, for 10 s), but not noradrenaline (0.03–30 μmol/l), were significantly greater in anococcygeus muscles from diabetic rats than from control rats (p <0.05). NOLA (100 μmol/l) significantly enhanced stimulation-induced contractions (p <0.05), however the enhancement was significantly less in tissues from diabetic rats (p <0.05). The results suggest that STZ-induced diabetes impairs smooth muscle reactivity to nitric oxide in the rat anococcygeus muscle.
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Abbreviations
- STZ:
-
Streptozotocin
- NOLA:
-
NG-nitro-l-arginine
- NANC:
-
nonadrenergic noncholinergic
- ANOVA:
-
analysis of variance
References
Hosking DJ, Bennett T, Hampton JR (1978) Diabetic autonomic neuropathy. Diabetes 27: 1043–1054
Clarke BF, Ewing DJ, Campbell IW (1979) Diabetic autonomic neuropathy. Diabetologia 17: 195–212
Lincoln J, Bokor JT, Crowe R, Griffith SG, Haven AJ, Burnstock G (1984) Myenteric plexus in streptozotocin-treated rats. Neurochemical and histochemical evidence for diabetic neuropathy in the gut. Gastroenterology 86: 654–661
Belai A, Lincoln J, Milner P, Crowe R, Loesch A, Burnstock G (1985) Enteric nerves in diabetic rats: increase in vasoactive intestinal polypeptide but not substance P. Gastroenterology 89: 967–976
Belai A, Lincoln J, Burnstock G (1987) Lack of release of vasoactive intestinal polypeptide and calcitonin gene-related peptide during electrical stimulation of enteric nerves in streptozotocin-diabetic rats. Gastroenterology 93: 1034–1040
Belai A, Lincoln J, Milner P, Burnstock G (1988) Progressive changes in adrenergic, serotonergic, and peptidergic nerves in proximal colon of streptozotocin-diabetic rats. Gastroenterology 95: 1234–1241
Nowak TV, Harrington B, Kalbfleisch JH, Amatruda JM (1986) Evidence for abnormal cholinergic neuromuscular transmission in diabetic rat small intestine. Gastroenterology 91: 124–132
Nowak TV, Harrington B, Kalbfleisch J (1990) Adaptation of cholinergic enteric neuromuscular transmission in diabetic rat small intestine. Diabetes 39: 891–897
Mathison R, Davison JS (1988) Modified smooth muscle responses of jejunum in streptozotocin-diabetic rats. J Pharmacol Exp Ther 244: 1045–1050
Longhurst PA, Belis JA (1986) Abnormalities of rat bladder contractility in streptozotocin-induced diabetes mellitus. J Pharmacol Exp Ther 238: 773–777
Longhurst PA (1990) The effects of testosterone or insulin treatment on contractile responses of the rat vas deferens following castration or streptozotocin-induced diabetes mellitus. Gen Pharmacol 21: 427–434
MacLeod KM, McNeill JH (1985) The influence of chronic experimental diabetes on contractile responses of rat isolated blood vessels. Can J Physiol Pharmacol 63: 52–57
Belai A, Lefebvre RA, Burnstock G (1991) Motor activity and neurotransmitter release in the gastric fundus of streptozotocin-diabetic rats. Eur J Pharmacol 194: 225–234
D'Amato M, Currò D (1990) Non-adrenergic non-cholinergic inhibitory innervation of the gastric fundus in streptozotocin-diabetic rats. Acta Physiol Hung 75 [Suppl]: 77–78
Rand MJ (1992) Nitrergic transmission: nitric oxide as a mediator of non-adrenergic, non-cholinergic neuro-effector transmission. Clin Exp Pharmacol Physiol 19: 147–169
Oyama Y, Kawasaki H, Hattori Y, Kanno M (1986) Attenuation of endothelium-dependent relaxation in aorta from diabetic rats. Eur J Pharmacol 131: 75–78
Mayhan WG (1989) Impairment of endothelium-dependent dilatation of cerebral arterioles during diabetes mellitus. Am J Physiol 256: H621-H625
Taylor PD, McCarthy AL, Thomas CR, Poston L (1992) Endothelium-dependent relaxation and noradrenaline sensitivity in mesenteric resistance arteries of streptozotocin-induced diabetic rats. Br J Pharmacol 107: 393–399
Li CG, Rand MJ (1989) Evidence for a role of nitric oxide in the neurotransmitter system mediating relaxation of the rat anococcygeus muscle. Clin Exp Pharmacol Physiol 16: 933–938
Gillespie JS (1972) The rat anococcygeus muscle and its response to nerve stimulation and to some drugs. Br J Pharmacol 45: 404–416
Feelisch M (1991) The biochemical pathways of nitric oxide formation from nitrovasodilators: appropriate choice of exogenous NO donors and aspects of preparation and handling of aqueous NO solutions. J Cardiovasc Pharmacol 17 [Suppl 3]: S25-S33
Luheshi GN, Zar MA (1992) Effect of streptozotocin diabetes on motor and inhibitory transmission in rat anococcygeus. Can J Physiol Pharmacol 70: 1372–1378
Saenz de Tejada I, Goldstein I, Azadzoi K, Krane RJ, Cohen RA (1989) Impaired neurogenic and endothelium-mediated relaxation of penile smooth muscle from diabetic men with impotence. N Engl J Med 320: 1025–1030
Li CG, Rand MJ (1990) Nitric oxide and vasoactive intestinal polypeptide mediate non-adrenergic, non-cholinergic inhibitory transmission to smooth muscle of the rat gastric fundus. Eur J Pharmacol 191: 303–309
Kim N, Azadzoi KM, Goldstein I, Saenz de Tejada I (1991) A nitric oxide-like factor mediates nonadrenergic-noncholinergic neurogenic relaxation of penile corpus cavernosum smooth muscle. J Clin Invest 88: 112–118
Rajfer J, Aronson WJ, Bush PA, Dorey FJ, Ignarro LJ (1992) Nitric oxide as a mediator of relaxation of the corpus cavernosum in response to nonadrenergic, noncholinergic neurotransmission. N Engl J Med 326: 90–94
Waldman SA, Murad F (1987) Cyclic GMP synthesis and function. Pharmacol Rev 39: 163–196
Bucala R, Tracey KJ, Cerami A (1991) Advanced glycosylation products quench nitric oxide and mediate defective endothelium-dependent vasodilatation in experimental diabetes. J Clin Invest 87: 432–438
Vlassara H, Fuh H, Makita Z, Krungkrai S, Cerami A, Bucala R (1992) Exogenous advanced glycosylation end products induce complex vascular dysfunction in normal animals: a model for diabetic and aging complications. Proc Natl Acad Sci USA 89: 12043–12047
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Way, K.J., Reid, J.J. Nitric oxide-mediated neurotransmission is attenuated in the anococcygeus muscle from diabetic rats. Diabetologia 37, 232–237 (1994). https://doi.org/10.1007/BF00398048
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DOI: https://doi.org/10.1007/BF00398048