4. Disscution
Nicorandil is a safe, well-known antianginal agent that has been approved as a long-term therapy for angina in Japan and Europe6. The Japanese Coronary Artery Disease (CAD) and the Impact of Nicorandil in Angina studies have revealed a beneficial impact for Nicorandil on mortality and morbidity in patients with CAD7,8.The use of Nicorandil has been recommended by the European Society of Cardiology as one of the second-line treatments for chronic stable angina1. Overall, comparative clinical trials have shown an equivalent efficacy of Nicorandil in improving effort angina and ischemic symptoms compared to β blockers and calcium antagonists with minimal hemodynamic disturbance9. Interestingly, a meta-analysis from 17 clinical trials has demonstrated that Nicorandil treatment ameliorated left ventricular ejection fraction and microvascular function when used in patients with acute myocardial infarction (AMI) in conjugation with coronary reperfusion therapy10.Long-term therapy of Nicorandil also showed beneficial effects on left ventricular remodeling and sympathetic nerve activity of myocardium in patients with AMI when used after reperfusion therapy11. In addition, Nicorandil treatment when used as adjunctive to coronary angioplasty was accompanied by better clinical and functional outcomes in patients with anterior AMI compared to angioplasty alone. This was mainly attributed to a decrease in myocardial injury and improvement in microvascular function and rate of no-reflow12. Another study revealed that intravenous nicorandil reduced QT dispersion and ventricular fibrillation in patients after successful coronary angioplasty13. But few studies had repored that Intravenous Nicorandil intake was associated with significant drop in blood pressure. While,in our research, we found Intravenous Nicorandil could significantly reduce systolic and diastolic blood pressure in patients without affecting heart rate, and it reduced in depending on concentrations. Other than that, several reports demonstrated that Nicorandil may cause severe vasodilation and fall in blood pressure when used preoperatively before coronary artery bypass graft14. So we can speculate that Nicorandil, like nitroglycerin, may relieve angina and affect blood pressure at the same time.
The vasodilating effect of Nicoradil is relate to the effect of opening the ATP-sensitive K channel, as well as to the effect of increasing production of cGMP4. ATP-sensitive K channel which not only exists in coronary endothelium, but also in peripheral vascular smooth muscle cells15. Probablely,Nicoradil may activate and open ATP-sensitive K channel of the cell membrane of vascular smooth muscle cells, thus promote the potassium efflux, which leads to vascular smooth muscle cell membrane hyperpolarization. Furthermore, T-type voltage-dependent calciumion channel is closed, reducing intracellular calciumion concentration and inhibiting vascular smooth muscle contraction, therefore affects blood pressure16. Meanwhile, Nicoradil can activate guanine cyclase17, which could increase cGMP in smooth muscle and other tissues, resulting in dephosphorylation of myosin light chain, regulating vascular smooth muscle contraction, peripheral vein dilatation, blood retention in the peripheral, decreasing re-turned blood volume and left ventricular end diastolic pressure (LVEDP), dilating the artery reduces peripheral resistance. Arteriovenous dilation reduces myocardial oxygen consumption and relieves angina, so it may also decrease blood pressure.