Bradykinin and Human Forearm Metabolism: Inhibition of Endogenous Prostaglandin Synthesis

Abstract

The metabolism of the human forearm was studied in healthy volunteers by the registration of arterial and deep-venous concentrations of oxygen and glucose and of resting forearm blood flow during the intrabrachial arterial infusion of 0.9% NaCl (n = 4), papaverine (n = 5), bradykinin (n = 9) and bradykinin after the oral pretreatment with indomethacin, an inhibitor of prostaglandin synthesis (n = 10). The blood flow was not affected during the infusion of NaCl (0.2 m//min) but was increased, depending on the concentrations, 2-and 3-fold during infusion of papaverine (2 or 3 /ig/(kg χ min)), and 2-fold during infusion of bradykinin (0.2 ng/(kg χ min)).The latter effect on the blood flow was significantly smaller when endogenous synthesis of prostaglandins was impaired by indomethacin pretreatment. Arterial oxygen and glucose concentrations were maintained during the individual infusions. This was also true for the arterial-deepvenous concentration differences of oxygen and glucose during NaCl infusions. Corresponding to the acceleration of the blood flow caused by papaverine and bradykinin, arterial-deep-venous concentration oxygen differences declined, indicating that oxygen consumption of the muscle was not changed. A similar behaviour was observed for muscukr extraction and consequently uptake of glucose when the acceleration of the blood flow was caused by papaverine. In contrast, doubling of the blood flow caused by the infusion of bradykinin was accompanied with enlargement of the arterial-deep-venous concentration difference and thus of muscular glucose uptake. There was no change in the arterial and forearm deepvenous levels of insulin under these conditions. Also, this effect of bradykinin was nearly abolished after oral pretreatment with indomethacin. From these data one may suggest that bradykinin, besides its well-known action on blood flow, also affects the glucose metabolism of the human forearm apparently via endogenously synthetized prostaglandins. Bradykinin und Unterarmstoff wechsel: Hemmung der endogenen ProstaglandinSyntheseZusammenfassung: An gesunden Probanden wurde der Stoffwechsel des Unterarms studiert. Dazu wurden die arteriellen und tiefvenösen Konzentrationen von Sauerstoff und Glucose sowie der Unterarmdurchfluß gemessen. Dies geschah während einer Infusion von 0.9% NaCl (η = 4), von Papaverin (η = 5), von Bradykinin (n = 9) sowie von Bradykinin nach oraler Vorbehandlung mit Indomethacin, einem Inhibitor der Prostaglandin-Biosynthese (η = 10). Infusion von NaCl änderte den Unterarmdurchfluß nicht, während Papaverin (2 und 3 μ% χ kg -1 χ min -1 ) ihn kon-

Insulin action on glucose uptake into skeletal muscle

“…There are other findings which favour this view. Prostaghurdins are known to exhibit insulinlike activity in myocardial [ 18-201 and adipose tissue [2 1,221 . Furthermore, kinins, the most likely candidates for the muscular activity factor [2,3,23] (which themselves display insulin-like activity [4,24]) are no longer effective ifprostaglandin synthesis is blocked by indomethacin [4] . Further support has come from the finding that prevention of endogenous kinin liberation by a kallikrein inhibitor also reduced the action of insulin on glucose uptake into the human forearm [ 11.…”

“…Further support has come from the finding that prevention of endogenous kinin liberation by a kallikrein inhibitor also reduced the action of insulin on glucose uptake into the human forearm [ 11. That insulin, in contrast to kinins [4,25] and prostaglandins [26] , did not accelerate blood flow ([13,14] table 2) would not speak against such a notion, since insulin exhibits its actions only in insulin-sensitive tissues where the hormone is bound to specific receptors [271.…”

“…All the subjects fasted overnight and received no special premeditation. The catheterization procedure was detailed in [3,4]. Arterial and deep-venous blood samples were collected simultaneously at 5 mm intervals throughout 15 min basal period followed by a 30 min infusion period for chemical analysis.…”

“…A crucial role of kinin liberation has been demonstrated for the acceleration of glucose uptake which occurs during muscle work [2] and hypoxia [3]. Since evidence had been obtained [4] that the effect of kinins on glucose uptake into muscle was mediated via the synthesis of prostaglandins, it was of interest to investigate whether insulin action on glucose uptake into skeletal muscle of the human forearm might be impaired after indomethacin pretreatment which prevents prostaglandin synthesis in man [S].…”

“…Three minutes after the start of insulin infusion, 1 mg glucose/kg body wt/min was infused into an anticubital vein in group 1. Forearm blood flow was estimated by venous-occlusion plethysmography [6,7] as detailed in [4].…”