We previously demonstrated that
uridine adenosine tetraphosphate (
Up4A) exerts a potent
vasodilator effect in the healthy porcine coronary vasculature. Since the coronary microvascular effects of
Up4A after
myocardial infarction (MI) are unknown, the present study investigated the response to
Up4A in coronary microvessels from post-MI remodeled porcine myocardium, and the involvement of
purinergic receptor subtypes. Coronary small arteries (diameter ∼150 μm) were dissected from the apex of
Sham-operated swine and swine in which MI had been produced 5 weeks earlier by transient (2h) occlusion of the left circumflex coronary artery, and mounted on Mulvany wire myographs.
Up4A (10(-9)-10(-5)M) produced coronary vasodilation that was reduced in MI as compared to
Sham-operated swine. Up4A-induced vasodilation was reduced by P1 blockade with
8-phenyltheophylline in
Sham-operated swine and to a lesser extent in MI, while the attenuation by the A2A receptor blocker
SCH58261 was similar in
Sham-operated and MI swine. Up4A-induced vasodilation remained unaffected by non-selective P2 receptor antagonist
PPADS, but was attenuated by selective P2X1 and
P2Y1 receptor antagonists
MRS2159 and
MRS2179, albeit to a similar extent in
Sham-operated and MI swine. These responses were paralleled by similar
mRNA expression levels of A2A, P2X1 and
P2Y1 receptors in MI compared to slaughterhouse control swine. Finally, attenuation of Up4A-induced coronary vasodilation by
nitric oxide synthase inhibition was not attenuated in MI as compared to
Sham-operated swine. In conclusion, blunted coronary vasodilation in response to
Up4A in MI swine is most likely due to reduced activation of P1, rather than P2, receptors and does not involve a loss of NO bioavailability.