Cyclooxygenase 2 contributes to bradykinin-induced microvascular responses in peripheral arterioles after cardiopulmonary bypass

Abstract

Introduction Diabetic patients are associated with impaired peripheral microvascular function after cardiopulmonary bypass (CPB) and cardiac surgery. We hypothesized that upregulation of the inducible cyclooxygenase 2 (COX-2) contributes to altered microvascular reactivity of peripheral arterioles in diabetic patients undergoing CPB and cardiac surgery. Methods Skeletal muscle samples of non-diabetic (ND) and diabetic (DM) patients (n = 8/group) undergoing cardiac surgery were harvested before and after CPB. The protein expression/localization of COX-2 was assayed by Western blotting and immunohistochemistry. Peripheral arterioles were dissected from the harvested skeletal muscle tissue samples, the isolated arterioles (80–180μm) were cannulated and pressurized, and changes in diameter were measured with video microscopy. In-vitro relaxation responses of pre-contracted arterioles were examined in the presence of the endothelium-dependent vasodilator bradykinin (10−10 to 10−6M) and in the presence or absence of the selective COX-2 inhibitor NS398 (10−5M). Results The post-CPB protein levels of the inducible COX-2 were significantly increased compared with pre-CPB values in both the ND and DM groups (P<0.05), whereas, this increase was higher in DM than that of non-diabetics (P<0.05). In the DM arterioles, not the ND vessels, bradykinin-induced relaxation response was inhibited in the presence of the specific COX-2 inhibitor NS398 at baseline (P<0.05). After CPB, bradykinin-induced relaxation response of the ND and DM arterioles was inhibited in the presence of the specific COX-2 inhibitor NS398, but this effect was more pronounced in the diabetic patients (P<0.05). Conclusion Diabetes and CPB are associated with up-regulation in COX-2 expression/activation in human peripheral microvasculature. This alteration may lead to altered peripheral microvascular reactivity in diabetic patients undergoing cardiac surgery.

A Network Pharmacology Technique to Investigate the Synergistic Mechanisms of Salvia miltiorrhiza and Radix puerariae in Treatment of Cardio‐Cerebral Vascular Diseases

“…As shown in Figure 4 , the highest value of the degree of the target interacting with the ingredients is PTGS2. In addition, PTGS2, called cyclooxygenase 2, is an important enzyme in the biosynthesis of prostaglandins, which has both a dioxygenase and a peroxidase [ 46 ]. Thus, SM and RP synergistically effect with PI3K-Akt, TNF, and Jak-STAT signaling pathways and PTGS2 targets to treat CCVDs.…”

Decreased contractile response of peripheral arterioles to serotonin after CPB in patients with diabetes

“…18,19 Furthermore, there is an increase in COX-2 expression/activation in peripheral arterioles of patients post-CPB compared to pre-CPB and this increase is higher in patients with diabetes compared to patients without diabetes. 20 These changes may contribute to the altered peripheral microvascular reactivity to serotonin in patients with diabetes following cardiac surgery and CPB.…”