Effect of Experimental Diabetes, Food Deprivation and Genetic Obesity on the Sensitivity of Pithed Rats to Autonomic Agents

Abstract

I The sensitivities of alloxan and streptozotocin diabetic and hereditary obese pithed rats to acetylcholine, isoprenaline and noradrenaline were compared to those of controls. 2 Blood pressure and heart rate recordings made before dosing was started showed the streptozotocin-treated animals to have a significantly reduced heart rate and increased pulse pressure as compared with controls.3 Both diabetic groups were found to have reduced sensitivities to the pressor effect of noradrenaline, the depressor effect of acetylcholine, the positive chronotropic and inotropic effect of isoprenaline and the reduction in diastolic pressure induced by isoprenaline. The reduction in sensitivity was generally much greater in the streptozotocin diabetic animals. 4 The genetically obese rats were found to have similar sensitivities to all three agents as did their non-obese litter mates. 5When either diabetic group was deprived of food for 24 h preceding the tests the sensitivities were found to be raised significantly towards normal in almost all cases. 6 The results are contrasted with previous in vitro results and possible causative metabolic factors discussed. It is suggested that sensitivity changes are unevenly distributed within the cardiovascular system.

Cardiovascular Effects of Alloxan Diabetes in Normotensive and Spontaneously Hypertensive Rats

“…Both hypertensive and normo tensive diabetic animals exhibited significantly reduced pressor responses in comparison to their age-matched controls. Foy and Lucas (17), using pithed normotensive rats only 1 week after alloxan, found similar reductions in vascular sensitivity to vasoactive agents. On the other hand, responses of the isolated atrial and aortic preparations taken from diabetic WKY and control preparations were not readily dis sociable.…”

“…Placing the tissues in fresh physiological solution may restore them to a more normal environment, by washing out toxic metabolites or by avoiding impaired metabolic pathways. Foy and Lucas (17) have suggested that hyperglycemia per se may be one cause of the reduced sensitivity, since starvation of subsequently pithed diabetic rats normalized the responses to various vasoactive agents. In addition, Malik and McGiff (28), using high glucose perfusate, have reported reductions in constrictor responses in perfused rat mesen teries.…”

“…Furthermore. Foy and Lucas (17) demonstrated in the pithed alloxan-diabetic rat a reduction in the pressor response to norepinephrine, in the depressor response to acetylcholine and in the positive chronotropic and inotropic actions of isopro terenol. The differences in vascular reactivity may be attributed to variations in species and diabetogen used.…”

Alterations in alpha1-adrenoceptor stimulation of isolated atria from experimental diabetic rats

“…Foy and Lucas (1 976) demonstrated that the chronotropic response of both alloxan (1 week) and ' control rats. In direct contrast, these authors obsened an increase in the chronotropic response of isolated spontaneously beating right atria from streptozotocin-diabetic rats (2 weeks) to both norepinephrine and isoproterenol (Foy and Lucas 1978). Ingebretsen et al (1980) observed no difference in the inotropic response of isolated working hearts from alloxan-diabetic (72 h) rats to isoproterenol.…”

Profile of Endothelin Isopeptides and Markers of Oxidative Stress Alongside the Onset of Streptozotocin-Type I Diabetes in Rats

“…4 The depressed blood pressure and pacemaker function (heart contractility) we observed over the 21 dayonset of diabetes were previously reported in this rat model for up to 6-7 weeks. [14][15][16][17][18][19] Thus, the prevalence of hypertension in the diabetic population, an important risk factor for atherosclerosis, is not met in such a short period of time. Indeed, chronic hypertension in the STZ rat model was only observed after diabetes had been present for 20 weeks.…”