Abstract
Diabetes was induced in rats by a single intraperitoneal injection of streptozotocin (65 mg kg-1). Rabbits were rendered diabetic by injecting alloxan (100 mg kg-1) into the lateral ear vein. Diabetes was confirmed by a significant elevation of serum glucose in both species 8 weeks after injection. The maximum contraction to noradrenaline (NA), 5-hydroxytryptamine (5-HT) and KCl was markedly diminished in thoracic aortic rings (AR) from diabetic rats with no change in the EC50 of the agonists. There were no differences in the contractile properties of AR from diabetic rabbits to NA, 5-HT or KCl. Diabetes did not alter the responsiveness of AR from the rat to angiotensin II (AII). However, AR from diabetic rabbits displayed a decreased maximal contraction and an increased EC50 to AII. The magnitude of the acetylcholine-induced relaxation to precontracted AR was not different between diabetic and control rats and rabbits. The contractile responses of AR to NA, 5-HT and KCl were depressed in diabetic rats, regardless of the control tissue to which they were compared. The decrease in maximal contraction to NA, 5-HT and KCl seen in diabetic animals was prevented by insulin replacement. The results demonstrated that while both rats and rabbits exhibited a similar degree of hyperglycemia after treatment with a diabetogenic agent, aortic preparations from the rabbit are not affected in the same way as the aorta from the diabetic rat when exposed to NA, 5-HT and KCl. This feature may be related to the marked differences between the extent of sympathetic innervation of the aorta in the rabbit and rat. Furthermore, the decrease in maximal contraction in rat aorta was non-specific with respect to agonists since it could also be demonstrated with KCl. Therefore, it follows that the diabetic state may affect processes responsible for contraction beyond the level of receptor activation.
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- Christlieb A. R. Diabetes and hypertensive vascular disease. Mechanisms and treatment. Am J Cardiol. 1973 Sep 20;32(4):592–606. doi: 10.1016/s0002-9149(73)80051-7. [DOI] [PubMed] [Google Scholar]
- Clements R. S., Jr, Morrison A. D., Winegrad A. I. Polyol pathway in aorta: regulation by hormones. Science. 1969 Nov 21;166(3908):1007–1008. doi: 10.1126/science.166.3908.1007. [DOI] [PubMed] [Google Scholar]
- Cohen M. L., Berkowitz B. A. Age-related changes in vascular responsiveness to cyclic nucleotides and contractile agonists. J Pharmacol Exp Ther. 1974 Oct;191(1):147–155. [PubMed] [Google Scholar]
- Cryer P. E., Silverberg A. B., Santiago J. V., Shah S. D. Plasma catecholamines in diabetes. The syndromes of hypoadrenergic and hyperadrenergic postural hypotension. Am J Med. 1978 Mar;64(3):407–416. doi: 10.1016/0002-9343(78)90220-6. [DOI] [PubMed] [Google Scholar]
- Fleming W. W., Westfall D. P., De la Lande I. S., Jellett L. B. Log-normal distribution of equiefective doses of norepinephrine and acetylcholine in several tissues. J Pharmacol Exp Ther. 1972 May;181(2):339–345. [PubMed] [Google Scholar]
- Fortes Z. B., Garcia Leme J., Scivoletto R. Vascular reactivity in diabetes mellitus: role of the endothelial cell. Br J Pharmacol. 1983 Jul;79(3):771–781. doi: 10.1111/j.1476-5381.1983.tb10016.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Head R. J., Hempstead J., Berkowitz B. A. Catecholamines in the vasculature of the rat and rabbit: dopamine, norepinephrine, epinephrine. Blood Vessels. 1982;19(3):135–147. [PubMed] [Google Scholar]
- Lazar M., Golden P., Furman M., Lieberman T. W. Resistance of the rabbit to streptozotocin. Lancet. 1968 Oct 26;2(7574):919–919. doi: 10.1016/s0140-6736(68)91094-5. [DOI] [PubMed] [Google Scholar]
- Longhurst P. A., Head R. J. Responses of the isolated perfused mesenteric vasculature from diabetic rats: the significance of appropriate control tissues. J Pharmacol Exp Ther. 1985 Oct;235(1):45–49. [PubMed] [Google Scholar]
- MacLeod K. M., McNeill J. H. Alpha adrenoceptor mediated responses in aorta from three month streptozotocin diabetic rats. Proc West Pharmacol Soc. 1982;25:245–247. [PubMed] [Google Scholar]
- Moorhouse J. A., Carter S. A., Doupe J. Vascular responses in diabetic peripheral neuropathy. Br Med J. 1966 Apr 9;1(5492):883–888. doi: 10.1136/bmj.1.5492.883. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Owen M. P., Carrier G. O. Alteration in vascular smooth muscle sensitivity to vasoconstrictor agents by streptozotocin induced diabetes. Proc West Pharmacol Soc. 1979;22:363–366. [PubMed] [Google Scholar]
- Owen M. P., Carrier G. O. Calcium dependence of norepinephrine-induced vascular contraction in experimental diabetes. J Pharmacol Exp Ther. 1980 Feb;212(2):253–258. [PubMed] [Google Scholar]
- Pfaffman M. A., Ball C. R., Darby A., Hilman R. Insulin reversal of diabetes-induced inhibition of vascular contractility in the rat. Am J Physiol. 1982 Apr;242(4):H490–H495. doi: 10.1152/ajpheart.1982.242.4.H490. [DOI] [PubMed] [Google Scholar]
- Pfaffman M. A., Hilman R., Darby A. Contractile and relaxing activity of arterial smooth muscle from streptozotocin-diabetic rats. Res Commun Chem Pathol Pharmacol. 1980 Nov;30(2):283–299. [PubMed] [Google Scholar]
- RAKIETEN N., RAKIETEN M. L., NADKARNI M. R. Studies on the diabetogenic action of streptozotocin (NSC-37917). Cancer Chemother Rep. 1963 May;29:91–98. [PubMed] [Google Scholar]
- Ramanadham S., Lyness W. H., Tenner T. E., Jr Alterations in aortic and tail artery reactivity to agonists after streptozotocin treatment. Can J Physiol Pharmacol. 1984 Apr;62(4):418–423. doi: 10.1139/y84-066. [DOI] [PubMed] [Google Scholar]
- Scarborough N. L., Carrier G. O. Increased alpha 2-adrenoreceptor mediated vascular contraction in diabetic rats. J Auton Pharmacol. 1983 Sep;3(3):177–183. doi: 10.1111/j.1474-8673.1983.tb00533.x. [DOI] [PubMed] [Google Scholar]
- Scarborough N. L., Carrier G. O. Nifedipine and alpha adrenoceptors in rat aorta. II. Role of extracellular calcium in enhanced alpha-2 adrenoceptor-mediated contraction in diabetes. J Pharmacol Exp Ther. 1984 Dec;231(3):603–609. [PubMed] [Google Scholar]
- Sullivan S., Sparks H. V. Diminished contractile response of aortas from diabetic rabbits. Am J Physiol. 1979 Feb;236(2):H301–H306. doi: 10.1152/ajpheart.1979.236.2.H301. [DOI] [PubMed] [Google Scholar]
- Turlapaty P. D., Lum G., Altura B. M. Vascular responsiveness and serum biochemical parameters in alloxan diabetes mellitus. Am J Physiol. 1980 Dec;239(6):E412–E421. doi: 10.1152/ajpendo.1980.239.6.E412. [DOI] [PubMed] [Google Scholar]