The effects of endothelium-dependent vasodilators on cardiac output and their distribution in the anaesthetized rat: a comparison with sodium nitroprusside.

1. The effects of sodium nitroprusside, acetylcholine and bradykinin on cardiac output and its distribution were studied in the anaesthetized, vagotomised rat preparation by use of 113Sn-labelled microspheres. 2. All three vasodilators lowered peripheral arterial blood pressure, but only bradykinin significantly reduced total peripheral resistance without reducing cardiac output. Bradykinin caused tachycardia, but this was offset by a reduction in stroke volume. These effects of bradykinin were not altered by indomethacin (4 mg kg-1). Acetylcholine and sodium nitroprusside both caused significant (P less than 0.05) reductions in stroke volume and cardiac output. 3. Bradykinin reduced vascular resistance in the liver, stomach, small intestine, large intestine, pancreas/mesentery, epididimides, skeletal muscle and fat. These responses were not affected by indomethacin, whereas, the reduction in vascular resistance in the brain induced by bradykinin was abolished by indomethacin. 4. Acetylcholine caused a reduction in renal vascular resistance, where bradykinin had no effect. However, acetylcholine did not cause any haemodynamic changes in the bradykinin-sensitive intestinal vasculature. 5. Acetylcholine caused vasoconstriction in the coronary and epididymal vasculature. Bradykinin in the presence of indomethacin induced vasoconstriction in the skin. 6. In conclusion, the data show that, with the possible exception of the brain and the skin, the vasodilator actions of bradykinin can adequately be transduced (presumably by endothelium-derived relaxing factor, EDRF) in the absence of prostacyclin synthesis. Additionally, these results indicate that the vasculature of the stomach, pancreas/mesentery, epididimides and skeletal muscle are equally sensitive to both acetylcholine and bradykinin, whereas the kidneys showed selectivity towards acetylcholine and the intestines towards bradykinin. These results may indicate differential receptor populations.