Hypersensitivity to methoxamine in atria isolated from streptozotocin‐induced diabetic rats

Abstract

1 The reactivity to methoxamine (Met) of atria isolated from the hearts of normal and from acutely streptozotocin-diabetic rats has been studied. 2 Met (1 x 10-6M) increased the tension of both normal and diabetic atria, but in diabetic atria, the dose-response curve to Met was shifted to the left and the efficacy of Met was enhanced. 3 Inhibitors of ca-adrenoceptors blocked, in a competitive manner, the positive inotropic effect induced by Met in both types of atrial preparations. 4 Inhibitors of the cyclo-oxygenase pathway for arachidonic acid metabolism blocked the atrial response to Met in non-diabetic as well as in diabetic atria. The inhibition of prostacyclin synthetase prevented the effect of Met in normal atria, while blockers of thromboxane generation inhibited it in diabetic ones. 5 Agents that inhibit the activity of lipoxygenase(s) significantly reduced the positive inotropic action induced by Met in diabetic atria but failed to modify it in non-diabetic preparations. 6 These results show that diabetic atria are more sensitive to Met than normal atria. In diabetes the response to ca-adrenoceptor stimulation could be mediated by oxidative products generated via thromboxane synthetase and lipoxygenase(s) activities; whereas in normal preparations the action of Met may involve the release of prostacyclin.

Alterations in atrial reactivity in a strain of spontaneously diabetic rats

“…were twice as great in diabetics as in controls. More relevant to our work, Canga & Sterin-Borda (1986) were able to find an enhanced efficacy in tension development of left atria from streptozotocin-treated rats to a,-receptor stimulation. In addition, a study by Jackson et al (1986) showed that right atria from streptozotocin-treated rats produced a significantly greater increase in contraction rate in response to phenylephrine.…”

“…Heyliger et al (1982) demonstrated that methoxamine-stimulated increases in contractile force were significantly attenuated in diabetic preparations. In direct contrast, more recent investiga-tions have revealed an enhanced inotropic and chronotropic response to a-adrenoceptor stimulation in hearts from diabetic animals (Jackson et al, 1986;Canga & Sterin-Borda, 1986). All of the above animal studies have relied on chemical substances as diabetogenic agents.…”

Effects of Aldose Reductase Inhibition With Epalrestat on Diabetes‐induced Changes in Rat Isolated Atria

“…It is also unlikely that the loss of bodyweight of diabetic rats observed in the present study, and reported by Kofo-Abayomi and Lucas (1988), was responsible for the differences in basal atrial rate and force observed. However, other studies reporting similar changes (Foy & Lucas 1978) and no changes (Canga et al 1985;Canga & Sterin-Borda 1986;Austin & Chess-Williams 1991) in basal parameters did not document rat bodyweights, making it difficult to draw any conclusions.…”

“…slowly and with greater force than tissues from control rats (Foy & Lucas 1978;Kofo-Abayomi & Lucas 1988;Karasu et al 1990). However, other workers have found no changes in basal parameters (Canga et al 1985;Canga & Sterin-Borda 1986;Austin & Chess-Williams 1991). There are also conflicting reports regarding the sensitivity of rat isolated atria to the inotropic and chronotropic action of the fl-adrenoceptor agonist isoprenaline (Foy & Lucas 1978;Kofo-Abayomi & Lucas 1988;Durante et al 1989;Karasu et al 1990;Austin & Chess-Williams 1991;Yu & McNeill 199 1).…”

Renal Phospholipid Metabolism in Streptozotocin-lnduced Diabetic Rats

“…Weight-and age-matched control rats received injec tions o f citrate buffer, pH 4.5 [18], Rats were kept on food and water ad libitum. Rats were killed by decapitation 72 h (acute state) or 12 weeks (chronic state) after the induction o f diabetes [ 19].…”