EFFECTS OF ADENOSINE-A(2A) RECEPTOR AGONIST, CGS-21680, ON BLOOD-PRESSURE, CARDIAC INDEX AND ARTERIAL CONDUCTANCE IN ANESTHETIZED RATS

The effects of thyl)phenethylamino-5'-N-ethylcarboxamidoadenosine (CGS 21680) on blood pressure, total peripheral resistance, cardiac index, heart rate and arterial conductance in different vascular beds in the presence and absence of hexamethonium (ganglionic blocker) and phenyl ephrine (alpha(1)-adrenoceptor agonist) were investigated in pentobarb itone-anaesthetized rats using a radioactive microsphere technique. CG S 21680 (0.1, 0.3 and 1.0 mu g/kg/min) significantly decreased blood p ressure and total peripheral resistance, and increased heart rate and cardiac index. In addition, after infusion with CGS 21680 (0.1, 0.3 an d 1.0 mu g/kg/min) arterial conductance in coronary bed significantly increased. However, while CGS 21680 (0.3 and 1.0 mu g/kg/min) signific antly increased conductance in skeletal muscle, it significantly decre ased splenic arterial conductance. Moreover, CGS 21680 (1.0 mu g/kg/mi n) significantly increased conductance in cerebral arterial bed. Infus ion with hexamethonium (200 mu g/kg/min) resulted in significant reduc tion in blood pressure, heart rate and cardiac index whereas stroke vo lume and total peripheral resistance remained unchanged. In animals th at were pretreated with hexamethonium (200 mu g/kg/min), further admin istration of CGS 21680 (0.3 mu g/kg/min), compared to CGS 21680 alone, significantly reduced blood pressure, heart rate and cardiac index bu t did not affect total peripheral resistance or conductance in any vas cular bed. Administration of phenylephrine (7 mu g/kg/min) resulted in a significant increase in blood pressure and total peripheral resista nce, and a significant reduction in cardiac index and heart rate. In a nimals infused with phenylephrine and CGS 21680 combined, in compariso n to those animals that received CGS 21680 alone, no significant diffe rences in blood pressure, heart rate, total peripheral resistance, car diac index or conductance in any vascular beds were found. Our present findings suggest that CGS 21680 decreased blood pressure by decreasin g total peripheral resistance, and increased cardiac index possibly th rough a reflex-mediated increase in heart rate. Moreover the coronary arterial bed is the most sensitive and cerebral arterial bed is the le ast sensitive to the effects of CGS 21680. In addition, the autonomic nervous system did not appear to play a major role in the actions of C GS 21680 on arterial conductance, and there was no difference in the a ction of this compound in the states of normal and raised vascular ton e.