ATTENUATION OF DEPRESSOR RESPONSE INDUCED BY PLATELET-ACTIVATING-FACTOR AND ACETYLCHOLINE IN STREPTOZOTOCIN-INDUCED DIABETIC RATS

The in vivo and in vitro effects of platelet-activating factor (PAF, 1-O-hexadecyl-2-acetyl-sn-glycero-3-phosphorylcholine) and acetylcholine (ACh) on vascular relaxation responses were examined in streptozotocin-induced diabetic rats. Intravenous injection of PAF and ACh (0.03 to 10-mu-g/kg) decreased the mean blood pressure in both control and diabetic rats in a dose-dependent fashion. Initial blood pressure in diabetic rats did not significantly differ from that in control rats. However, depressor responses induced by PAF and ACh in diabetic rats were attenuated more than those in control rats. In perfused mesenteric arterial bed preconstricted with methoxamine (10(-5) - 10(-4) M), PAF (10(-11) - 3 x 10(-10) M) produced a concentration-dependent relaxation. However, this relaxation was significantly attenuated in the diabetic preparation compared with the control preparation. ACh also produced a concentration-dependent vasodilation in perfused mesenteric arterial bed. The concentration-response curve for the relaxation of the mesenteric arterial bed to ACh in diabetic preparation was shifted to the right compared with that in control preparation. A pretreatment with oxyhaemogloblin (10(-6) M) also shifted the concentration - response curves for relaxation to ACh in both control and diabetic preparation to the right. There was no difference in relaxation induce by sodium nitroprusside between the diabetic and the control preparation. From the present results and previous work, which PAF showed an endothelium-dependent vasodilation in the perfused mesenteric arterial bed, it is suggested that impairment of endothelium-dependent relaxation in the perfused mesenteric arterial bed of diabetic rats may account, in part, for the attenuation of PAF- and ACh-induced depressor effect observed in diabetic rats in vivo.