Coronary microvascular actions of neuropeptide Y

ST-elevation myocardial infarction (STEMI) results in high levels of cardiac sympathetic drive which is a prognostic indicator of poor outcome.

We have recently shown the sympathetic co-transmitter neuropeptide-Y (NPY) is released during STEMI and that coronary levels correlate with microvascular dysfunction after primary percutaneous coronary intervention (PPCI), which we suggest may lead to larger infarcts and worsening cardiac function.

The mechanisms responsible for microvascular dysfunction are unknown, but in addition to vasoconstriction, could include inhibition of vasodilation to MI-released coronary metabolic vasodilators.

The latter is of particular interest as all NPY receptors are at least partly coupled through Gi/o, while many coronary vasodilators’ receptors act via Gs.

Therefore, first we will establish the receptors and G-proteins activated by NPY during vasomotor responses in intraventricular micro-arteries.

In addition to formative experiments with rats, we will utilize a porcine model of STEMI from which we can pair post-MI in vivo coronary NPY levels and infarct size to the ex vivo vasomotor actions of NPY, both vasoconstriction and block of Gs-dilation; with sham-operated pigs as controls.

Our unique, combined in vivo and ex vivo approaches will develop the possibility of drugs targeting NPY signalling pathways as an effective novel adjunct to PPCI.