Interference of converting enzyme inhibitors with the kallikrein-kinin system.
The unstimulated rat submandibular gland releases kallikrein into the circulation. This release is greatly increased by sympathetic nervous stimulation of the gland. We studied the effect of an angiotensin I converting enzyme (ACE) inhibitor (captopril) on blood flow of the unstimulated submandibular gland, and the effect of the ACE inhibitor on blood kinins and blood pressure of rats with prior sympathetic stimulation of the gland. To minimize the effects mediated by inhibition of angiotensin II formation, all rats were nephrectomized 48 hours before the studies. Administration of the ACE inhibitor caused a 2.4-fold increase in the blood flow of the unstimulated gland (p less than 0.001). Pretreatment with kinin antibodies diminished this increase by 86% (p less than 0.001). After sympathetic stimulation, blood flow to the gland increased five times, and kinin output in the venous effluent increased from 19 +/- 13 to 14,400 +/- 8,800 pg/min (p less than 0.001). Despite this conspicuous increase, arterial blood kinins did not change. Administration of the ACE inhibitor after stimulation of the gland resulted in a 10-fold increase in arterial blood kinins and in a pronounced decrease in blood pressure from 100 +/- 5 to 58 +/- 6 mmHg. This decrease was almost completely blocked by antibodies to either kallikrein or kinin. We concluded that the glandular kallikrein-kinin system may participate in the regulation of local blood flow in organs rich in glandular kallikrein such as the rat submandibular gland.(ABSTRACT TRUNCATED AT 250 WORDS)
D000806:Angiotensin-Converting Enzyme Inhibitors; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002216:Captopril / Q000494:pharmacology; D004702:Endocrine Glands / Q000378:metabolism; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D007610:Kallikreins / Q000378:metabolism*; D007705:Kinins / Q000097:blood / Q000378:metabolism*; D051381:Rats
D000806:Angiotensin-Converting Enzyme Inhibitors; D007705:Kinins; D002216:Captopril; D007610:Kallikreins