PURINERGIC RESPONSES IN THE FELINE PULMONARY VASCULAR BED

Adenosine and ATP produce dose-dependent, tone-dependent responses in the pulmonary vascular (PV) bed, under conditions of controlled pulmonary blood flow and constant left atrial pressure in vivo in intact-chest, spontaneously breathing cats. At low, resting PV tone, adenosine produces dose-dependent vasoconstrictor responses by acting on ''A1-like'' adenosine receptors which activate a phospholipase and thromboxane release. ATP produces dose-dependent vasoconstrictor responses, in part, following its metabolism to adenosine, by acting on ''A1-like'' adenosine receptors and by acting on P2X receptors. At elevated PV tone, data to date support that adenosine and ATP produce dose-dependent vasodilator responses by acting on A2 and P2Y receptors, respectively. Mechanisms to explain how a change in vascular tone alters the response of the vascular bed to a substance are not known. Moreover, the role of purinoceptors in pulmonary vascular disease is not known. Identification of selective pharmacological probes for purinoceptors in the pulmonary vascular bed is necessary to investigate their role in the development of pulmonary hypertension of acute and chronic lung disease.