Cardiovascular Sensitivity Changes to Eicosanoids in Rats With Experimentally Induced Diabetes Mellitus

Abstract

This paper attempts to provide a short review of the evidence for: 1. Increased platelet production of thromboxane A2 and reduced vascular production of prostacyclin in the human and also animal models of diabetes. 2. Reduced depressor responsiveness to arachidonic acid of anaesthetized alloxan- and streptozotocin-induced diabetic rats. 3. Enhanced constrictor responsiveness to arachidonic acid in blood-perfused hindquarters of alloxan-induced diabetic rats. 4. Potentiation by the thromboxane A2-mimetic, U46619, of constrictor responses to 5-hydroxytryptamine in Krebs'-perfused hindquarters and kidneys of both control and alloxan-induced diabetic rats. 5. Alterations during diabetes in production of, and responsiveness to, eicosanoids may contribute to the cardiovascular changes which occur in this disease.

Altered hypoxia-induced coronary vasodilatation in diabetic rabbit heart

“…†p < 0.05, compared with the three other groups. agreement with studies where the reduced vasodilatation during hypoxia in diabetes had been attributed to a diminution in the synthesis of endothelium-dependent vasodilating mediators such as NO and prostaglandin I 2 (Nakhostine and Lamontagne 1993;Park et al 1992;Gräser and Rubanyi 1992), thus unbalancing the vasodilator ability of the vessels and impairing myocardial microcirculation (Koltai et al 1992;Hodgson et al 1992). However, the reduced contribution of cyclooxygenase products seems to happen only during hypoxia since bradykinin-induced vasodilatation during normoxia in diabetic hearts was comparable with the one observed in normal rabbits (Nakhostine and Lamontagne 1994).…”

“…Recently, Nahser and co-workers (1995) demonstrated a reduced maximal coronary vasodilatation and an impaired coronary flow in response to increased heart demand in diabetic patients. Others confirmed these observations and proposed an imbalance in the production of relaxant and constrictor prostanoids and thromboxanes in diabetic animals (Koltai et al 1992;Hodgson et al 1992) and a perturbation in synthesis and release of vasoactive endothelial mediators (Shimokawa and Vanhoutte 1989). These data point to the endothelium as being severely injured in diabetes mellitus (Hsueh and Anderson 1992).…”

Effect of Male Sex and Obesity on Platelet Arachidonic Acid in Spontaneous Hypertensive Heart Failure Rats

“…Alterations in n-6 PUFA metabolism and subsequent increases in AA production can contribute to platelet hyper-reactivity and aggregation by providing increased substrate for the production of TXA 2 (6)(7)(8). This may result in a state of dynamic vasoconstriction and can exacerbate the transition to heart failure (8)(9)(10)(11)(12). Risk factors that are associated with alterations in PUFA metabolism, increases in AA production, and activation of platelets include obesity, diabetes, and aging (10,11,(14)(15)(16)(17)(18)(19)(20)(21).…”