Alteration of Purinergic Neurotransmission in Isolated Atria of Streptozotocin-induced Diabetic Rats

Abstract

Cardiac dysfunctions are described in diabetes. However, the role of purinergic neurotransmission in diabetes-related cardiovascular diseases is unknown. The purpose of this study was to evaluate the purinergic neurotransmission in isolated atria from streptozotocin-induced diabetic rats. The animals were grouped as control and diabetic with 30 days (D30) and 60 days (D60) after streptozotocin-induced diabetes. The isolated left and right atria were used in functional experiments. The effects of adenosine triphosphate, uridine diphosphate, and adenosine were evaluated on atrial inotropism and chronotropism. The antagonists 8-cyclopentyl-1,3-dipropylxanthine and pyridoxal-phosphate-6-azophenyl-2',4'-disulfonate were also used, as blockers of P1 and P2 receptors, respectively. A negative inotropic effect followed by a positive inotropic effect was induced by adenosine triphosphate in isolated atria. This negative inotropic effect was decreased by 25% in left atria of D30. Additionally, the apparent affinity for adenosine was diminished in left atria of D30, suggesting changes in P1 receptor function. No changes were found in the right atria of D30 stimulated by adenosine. The left atria and right atria stimulated by uridine diphosphate showed an increased inotropic effect of 92% and 17%, respectively. No changes were observed in left and right atria of D30 stimulated by uridine diphosphate. Our data showed the involvement of purinergic neurotransmission in diabetes-related cardiovascular changes.

Increase of angiotensin-converting enzyme activity and peripheral sympathetic dysfunction could contribute to hypertension development in streptozotocin-induced diabetic rats

“…This decreased purinergic response correlates well with a decreased similar response recently found in heart atria of STZ-treated rats. 5 As for the TR, we also found an apparent discrepancy between the vas deferens tonic contractions elicited by endogenous NA, which only elicited a mild increase in D60 (Figure 2(d)), and the drastic increase elicited by exogenous NA (Figure 3). Our data are only in partial agreement with the earlier observation of an increase of the purinergic and noradrenergic components of electrically induced vas deferens contractions of diabetic rats.…”

“…3 There are several theories that describe mechanisms related to the development of hypertension in diabetics. 1,4,5 For example, diabetic rats have a decrease in the levels of nitric oxide (NO) produced by acetylcholine in vascular endothelium and a higher incidence of oxidative stress in coronary arteries. 4 Common factors to diabetes and hypertension are oxidative stress and inflammation.…”

Cardiac purinergic signalling in health and disease

“…The maximum response of [Ca 2+ ] i to exogenous ATP was increased in diabetic cardiomyocytes [798]. Modulation of purinergic neurotransmission via P2YR in isolated atria of STZ-induced diabetic rats has been reported [799].…”

Obesity, Diabetes and Atrial Fibrillation; Epidemiology, Mechanisms and Interventions

“…Aberrant neurotransmission seems to be a key feature of arrhythmogenicity and a recently published study showed alterations in purinergic neurotransmission in the atria of diabetic rats [104]. AF may also be provoked in individuals with PAF and normal autonomic function by isoprenaline implying an increased susceptibility despite normal cardiovascular reflexes [105].…”