Histamine relaxation of aortic rings from diabetic rats

Abstract

The effect of histamine-induced relaxation on thoracic aortic rings from rats 5, 12, 24 and 52 weeks following streptozotocin-induced diabetes was determined. Preliminary studies confirmed the dependence of histamine-induced relaxation and the independence of nitroglycerin-relaxation (GTN) on the presence of endothelium (EDRF). Diabetes was confirmed by blood glucose levels exceeding 300 mg/dl. Rings with endothelium were depolarized several times with 50 mM KCL and then contracted with phenylephrine (10(-6)). Dose-response curves were plotted from data obtained following exposure to histamine (10(-7)-10(-3)) and GTN (10(-9)-10(-7)) and compared to responses from age-matched untreated controls, diabetic and diabetic rats treated with insulin (2 U/day). The relaxation produced by histamine on phenylephrine pre-contracted rings was similar in all three groups from 5-week age matched rats. However, histamine-induced relaxation from untreated diabetic rats was significantly depressed at 12, 24 and 52 weeks (p less than 0.001). Conversely there was no difference in the relaxation elicited by GTN on rings obtained from the three groups at any age. Pretreatment with diphenhydramine (5 x 10(-7)) on aortic rings from 12 and 52-week age matched rats resulted in qualitatively similar histamine dose-response curves that were displaced about two orders of magnitude to the right, indicative of H1 receptor competitive antagonism. These results demonstrate that the duration of diabetes alters the responsiveness of rat thoracic aortic rings to histamine but not to GTN and suggests that the responses elicited by certain agonists on target tissues may be significantly altered depending on the duration of diabetes.

Endothelial function in the isolated perfused mesentery and aortae of rats with streptozotocin‐induced diabetes: effect of treatment with the aldose reductase inhibitor, ponalrestat

“…diabetes (Oyama et al, 1986;Pieper & Gross, 1988;Durante et al, 1988;Tanz et al, 1989;Kamata et al, 1989;Cameron & Cotter, 1992a), but several have found no impairment (White & Carrier, 1986;Wakabayashi et al, 1987;Head et al, 1987;Gebremedhin et al, 1988;Mulhern & Docherty, 1989;Kappagoda et al, 1989). The explanation for these to the untreated diabetic group (pED50 [-log dose discrepant findings is not obvious, but variations in the duras)]: ARI-treated diabetic 9.90 ± 0.13, n = 18, versus tion and severity of diabetes and species differences, could be diabetic 9.87 ± 0.10, n = 20, NS) (Figure 3) on, ARI-treatment had no significant effect on The primary aim of this study was to determine whether line sensitivity in the aortae from diabetic rats the administration of the aldose reductase inhibitor, ponal-RI-treated diabetic 7.40 ± 0.06, versus 7.30 ± 0.06, restat, would prevent the development of endothelial dysr the untreated diabetic, NS) (Figure 4).…”

“…Functional studies in conduit arteries from animals with chemically induced diabetes have not been uniform in their findings, but impaired endothelium-dependent relaxation has been described (Oyama et al, 1986;Pieper & Gross, 1988;Durante et al, 1988; Kamata et al, 1989;Tanz et al, 1989;Mayhan, 1989;Abiru et al, 1990;Tesfamariam et al, 1990;Mayhan et al, 1991;Cameron & Cotter, 1992a), together with increased vascular reactivity to noradrenaline (MacLeod & McNeill, 1985;Harris & MacLeod, 1988;Piper & Gross, 1988;White & Carrier, 1988;Cohen et al, 1990). We have recently reported that resistance arteries from the mesenteric circulation of streptozotocin (STZ)-induced diabetic rats also display grossly impaired endothelium-dependent relaxation to acetylcholine, and an enhanced sensitivity to noradrenaline (Taylor et al, 1992).…”

Responses of the skin microcirculation to acetylcholine and sodium nitroprusside in patients with NIDDM

“…However, some preliminary data suggests that there are differences in the responses to acetylcholine and bradykinin in isolated resistance arteries from NIDDM patients, indicating that abnormalities of muscarinic receptors or specific G protein function may exist [15]. Observations in experimental diabetes indicate that specific receptor abnormalities are not responsible for the abnormal acetylcholine response in diabetes as impaired vasodilatation has been demonstrated to other endothelium-dependent vasodilators such as histamine which do not act via muscarinic receptors [30]. Although care should be taken when applying information from animal models to man, these findings suggest that other mechanisms may be responsible for the impaired acetylcholine response observed in NIDDM.…”

Enhanced, unaltered and impaired nitric oxide-mediated endothelium-dependent relaxation in experimental diabetes mellitus: importance of disease duration

“…Previous studies examining endothelium-dependent relaxation to acetylcholine or bradykinin due to streptozotocin (STZ)-induced diabetes have shown varying times of onset of impairment including: 1 week in intestinal arterioles [6], 2 weeks in hindquarters but not renal or femoral arteries [7], 3 weeks in cremaster muscle arterioles [8], 4±6 weeks in mesenteric arteries [9,10] or 4 weeks in aorta [11,12]. The variance in onset of endothelial dysfunction might be explained by experimental conditions including the type of artery or the type of vasodilator examined (e. g. histamine) in a given artery preparation [7,8,12,13]. Defects in endothelium-dependent relaxation which are specific for decreased nitric oxide (NO) bioactivity or NO production have not always been determined but have been confirmed and discussed [5].…”