Changes in Vascular Reactivity in Experimental Diabetic Rats: Comparison with Hypothyroid Rats

Abstract

The responsiveness to vasoactive agents in the perfused mesenteric vascular bed of streptozocin-induced diabetic rats was examined and compared with that of propylthiouracil-induced hypothyroid rats. Diabetic rats at 4 and 8 weeks after the induction of diabetes showed a significant decrease in isoproterenol-induced vasodilatation. In addition, the contractile responses to norepinephrine and 5-hydroxytryptamine and the vasodilative response to acetylcholine were significantly decreased in 12-week-diabetic rats. The contractile response to nerve stimulation was markedly decreased at 8 and 12 weeks. On the other hand, hypothyroid rats showed a decreased response to isoproterenol, but they did not show any change in the response to nerve stimulation. A decrease in plasma thyroid hormone levels in diabetic rats at any time period was similar in extent to that in hypothyroid rats. The data indicate that the progressive changes in vascular reactivity in diabetic rats may be divided into two stages. In the early stage, the altered reactivity of vasculature is likely to be mediated by hypothyroidism, whereas in the later stage, it is induced by other factors, e.g. hyperglycemia and hypoinsulinemia. Adrenergic neuropathy is not caused by hypothyroidism.

Impaired sensory‐motor nerve function in the isolated mesenteric arterial bed of streptozotocin‐diabetic and ganglioside‐treated streptozotocin‐diabetic rats

“…Other workers, also using the in vitro rat mesenteric arterial bed preparation, have shown that sympathetic neuropathy is a consequence of streptozotocin-induced diabetes (Longhurst & Head, 1985;Takiguchi et al, 1988). In these and our study rats were used at a similar time after induction of diabetes; however, in the former studies diabetes was induced in rats weighing (Cracco & Gabella, 1991).…”

“…Furthermore, these results are compatible with those of a recent in vivo study by Kiff et al (1991) who demonstrated raised mesenteric vascular conductance in streptozotocindiabetic rats and no differences in endothelium-dependent vasodilatation to ACh. Attenuated relaxations to endothelium-dependent vasodilators, but generally unimpaired endothelium-independent relaxations have been demonstrated in clinical (De Tejada et al, 1989) and a variety of experimental (Takiguchi et al, 1988;Kamata et al, 1989;Mayhan, 1992;Miyata et al, 1992;Taylor et al, 1992) diabetes, while endothelium-independent relaxations are generally unimpaired. It is possible that diabetes affects the different components of the vasculature with a different time course, with neuropathy occurring before the onset of endothelial changes.…”

“…The pathogenesis of diabetic neuropathy has been extensively studied in the streptozotocin-treated rat, a model of insulin-dependent diabetes. In this model, sympathetic dysfunction is suggested by attenuated contractile responses due to stimulation of sympathetic nerves in the rat mesenteric bed (Takiguchi et al, 1988) and tail artery (Hart et al, 1988). Ultrastructural changes in sympathetic ganglia (Monckton & Pehowich, 1982) and neuronal deficits in tyrosine hydroxylase (the ratelimiting enzyme in the synthesis of noradrenaline) and 5-hydroxytryptamine (5-HT) specific to mesenteric perivascular sympathetic nerves (Webster et al, 1991) have also been seen.…”

Review of Alterations in Endothelial Nitric Oxide Production in Diabetes

“…Decreases in endothelium-dependent relaxation are a common feature in both conduit 9 -20 and resistance [21][22][23][24][25][26][27][28][29][30] arteries of chemically induced experimental diabetic animals (including rats, mice, rabbits, hamsters, and dogs). In two genetic models of IDDM, similar impaired relaxation has been documented in aorta [31][32][33] and mesenteric arteries 34,35 of diabetes-prone BB/Wor or BB/E rats and in aorta 36 and mesenteric arteries 37 of the diabetes-prone WBN/Kob rat.…”

Responses of cerebral arterioles to activation of beta-adrenergic receptors during diabetes mellitus.

“…10 The mechanism of impaired responses of the aorta to /3-adrenergic activation did not appear to be related to an alteration in cAMP, since relaxation of the aorta in response to forskolin was similar in nondiabetic and diabetic rats. 911 Thus, it appears that the mechanism of impaired relaxation of the aorta in diabetic rats in response to activation of /3-adrenergic receptors is related to a decreased density and/or affinity of /3-adrenergic receptors on vascular smooth muscle.…”