Influence of adenosine triphosphate on the isolated perfused mesenteric artery of the rabbit

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Abstract
The vascular effects of adenosine triphosphate (ATP) were examined in the isolated perfused mesenteric arteries of the rabbit. Bolus injections of ATP (1 × 10−8 to 10−6 mol) induced a dose-dependent vasoconstrictor response at resting perfusion pressure, while continuous perfusion with ATP briefly elicited a vasoconstrictor response which was not maintained. Perfusion with phentolamine (2.65 × 10−6 M, an α-adrenergic receptor blocker), indomethacin (8.37 × 10−6 M, an inhibitor of cyclooxygenase), atropine (1 × 10−7 M, a muscarinic receptor blocker), and hydralazine (2 × 10−4 M, a vascular smooth muscle inhibitor) for a period of 1 h had no effect on vasoconstrictor responses to ATP. However, pretreatment with reserpine (2 mg∙kg−1∙day−1 for 2 days), an agent which depletes catecholamines, potentiated responses to ATP. On the other hand, when vascular tone was increased with an isoosmotic 60 mM K+ depolarizing Krebs bicarbonate solution, bolus injections of ATP elicited a prominent dose-dependent vasoconstriction followed by a prominent vasodilation. The degree of vasodilation but not of vasoconstriction elicited by ATP was greater in small terminal arteries with branches (−4 M) for 1 – 2 h. The vasoconstrictor responses were potentiated while the vasodilator responses were inhibited significantly by perfusion with propranolol (3 × 10−6 M) and phentolamine (2.65 × 10−6 M) together for 1 h or by pretreatment with reserpine followed by cold storage at 2 °C for 24 h. Perfusion with 8-phenyltheophylline (4 × 10−6 M (8-PT), an adenosine receptor blocker) for 1 h significantly inhibited by the vasodilator responses to bolus injections of adenosine but not to ATP. Further, ATP but not adenosine elicited a much more prominent vasodilator response on norepinephrine (NE) induced tone than on 60 mM K+. These studies suggest that ATP may induce vasoconstriction independent of activation of α-adrenergic or muscarinic receptors or enhanced synthesis of prostaglandins. This vasoconstriction is resistant to the inhibitory influence of hydralazine. On the other hand, the vasodilator response to ATP may be mediated through its interactions with released or circulating norepinephrine.