POTENTIAL ROLE OF BRADYKININ IN FOREARM MUSCLE METABOLISM IN HUMANS

Using the euglycemic-hyperinsulinemic glucose clamp and the human fore arm technique, we have demonstrated that the improved glucose disposal rate observed after the administration of an angiotensin-converting e nzyme (ACE) inhibitor such as captopril may be primarily due to increa sed muscle glucose uptake (MGU). These results are not surprising beca use ACE, which is identical to the bradykinin (BK)-degrading kininase II, is abundantly present in muscle tissue, and its inhibition has bee n observed to elicit the observed metabolic actions via elevated tissu e concentrations of BK and through a BK B-2 receptor site in muscle an d/or endothelial tissue. These findings are supported by several previ ous studies. Exogenous BK applied into the brachial artery of the huma n forearm not only augmented muscle blood flow (MBF) but also enhanced the rate of MGU. In another investigation, during rhythmic voluntary contraction, both MBF and MGU increased in response to the higher ener gy expenditure, and the release of BK rose in the blood vessel, draini ng the working muscle tissue. Inhibition of the activity of the BK-gen erating protease in muscle tissue (kallikrein) with aprotinin signific antly diminished these functional responses during contraction. Applyi ng the same kallikrein inhibitor during the infusion of insulin into t he brachial artery significantly reduced the effect of insulin on gluc ose uptake into forearm muscle. This is of interest, because in recent studies insulin has been suggested to elicit its actions on MBF and M GU via the accelerated release of endothelium-derived nitric oxide, th e generation of which is also stimulated by BK in a concentration-depe ndent manner. This new evidence obtained from in vitro and in vivo stu dies sheds new light on the discussion of whether BK may play a role i n energy metabolism of skeletal muscle tissue.