Role of the kinin-kallikrein system in the vasodilator action of an angiotensin converting enzyme inhibitor (captopril) on the systemic resistance and capacitance vessels of dogs

We investigated the vasodilator effects of Captopril (CAP) on the systemic capacitance and resistance vessels by measuring changes in the mean circulatory pressure (MCP) and total peripheral resistance (TPR) that occurred in response to the intravenous injection of CAP (1 mg/kg) in open-chest dogs. The following five groups of dogs received CAP: (1) Group of untreated dogs, (2) TSA Group in which the dogs were subjected to total spinal anesthesia (TSA), (3) Ang II Group in which the dogs received a continuous intravenous infusion of angiotensin II (Ang II), (4) APR+Ang II Group in which the dogs received a continuous intravenous infusion of Ang II after pretreatment with aprotinin (APR, 25,000 K.I.E.), a kallikrein inhibitor, and (5) IND+APR+Ang II Group in which the dogs received a continuous intravenous infusion of Ang II after pretreatment with indomethacin (IND, 5 mg/kg), a prostaglandin synthesis inhibitor, and APR. 1) CAP significantly decreased TPR and MCP in the untreated Group. 2) CAP significantly decreased TPR and MCP in the TSA Group. There were no significant differences in percentage change of TPR (%ΔTPR) and percentage change of MCP (%ΔMCP) between the untreated and TSA Groups. 3) In the Ang II Group, CAP decreased the elevated TPR significantly, but hardly affected the elevated MCP. 4) CAP significantly decreased TPR without significant change in MCP in the APR+Ang II Group. The%ΔTPR was significantly smaller in this Group than in the Ang II Group. 5) CAP significantly decreased TPR without significant change in MCP in the IND+APR+Ang II Group. The%ΔTPR was significantly smaller in this Group than in the Ang II Group. When one compares the arterial system with the venous system, this study suggests that the kinin-kallikrein system activating action of CAP partly contributes to its vasodilator action on the systemic resistance vessels.