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.