Captopril Increases the Affinity of Bradykinin Receptor Binding Sites in Bovine Coronary Arterial Endothelial Cells

Abstract

In a radioligand binding study using bovine coronary artery endothelial cell membranes, captopril changed a single bradykinin (BK) binding site (Kd = 1.77 nM, Bmax = 60.2 fmol/mg protein) to high- (Kd = 0.68 pM, Bmax = 17.7 fmol/mg protein) and low- (Kd = 1.00 nM, Bmax = 72.5 fmol/mg protein) affinity binding sites. This effect was reversed by GppNHp. Captopril also enhanced BK-induced endothelium-dependent relaxation in saponin-treated coronary rings, and GppNHp partially suppressed this enhancement. These results suggest that captopril may affect BK receptors that couple to G-proteins.

Role of ACE and NEP in bradykinin-induced relaxation and contraction response of isolated porcine basilar artery

“…Two mechanisms were thought for the reasons of increases of pD 2 and pA 2 : (1) increases in affinities themselves of BK and B 2 -receptor antagonist to B 2 -receptors; (2) more complete inhibition of BK degradation. In bovine coronary arterial endothelial cells, captopril might induce high affinity binding site by changing the conformation of B 2 -receptors (Miyamoto et al 2000). The Hill coefficient of Scatchard plot of [ 3 H]BK in these cells was less than unity, indicating that the number of binding site of B 2 -receptors was not single.…”

“…This biphasic response is induced by release of endothelial nitric oxide (NO; relaxation) and prostaglandin H 2 (contraction) via activation of the endothelial B 2 -receptor (Miyamoto et al 1999). It is important to compare the affinities of BK and a B 2 -receptor antagonist for B 2 -receptors in the absence or presence of ACE and NEP inhibitors for evaluating the role of ACE and NEP on BK degradation, because we have shown that captopril increases the affinity of BK to B 2 -receptor binding sites in bovine coronary arterial endothelial cells (Miyamoto et al 2000). Recently, several dual inhibitors of ACE and NEP have been developed for the treatment of hypertension, myocardial ischemia and coronary artery occlusion (Fournié-Zaluski et al 1994;Chatelain et al 1998;Rastegar et al 2000).…”

Protective effect of proteins derived from Calotropis procera latex against acute inflammation in rat

“…For each inflammagen, a control group was included along with other groups where rats were treated with two different doses of LP, a standard anti‐inflammatory drug, diclofenac and respective antagonist ( n = 6 per treatment group, Winter et al ., ). In the case of bradykinin‐induced inflammation, all the animals were pretreated with captopril (5 mg kg −1 given subcutaneously) 1 h earlier to prevent its degradation (Miyamoto et al ., ). The paw volume was measured up to a fixed mark on the lateral malleolus using plethysmography before inducing inflammation (0 h reading) and then at different time intervals after injecting an inflammagen.…”

Characterization of EST Gene in the Bovine Corpus Luteum during the Estrous Cycle

“…The mRNA of TNFR1 was expressed in the bovine CL at all stages during the estrous cycle. The concentration of TNF in the bovine endometrium at the early luteal stage was lower than concentrations at other luteal stages ( Miyamoto et al, 2000 ). Local secretion of TNF-α in the bovine CL was higher at the late stage than during the mid-stage.…”

“…TNF, a nonglycosylated protein with a molecular mass of 17 kDa, first described as a tumoricidal factor produced by activated macrophages, has a lower concentration in the bovine endometrium during the early luteal stage than at other luteal stages ( Miyamoto et al, 2000 ). Extensive research during the last decade suggests that TNF plays one or more physiological roles in the CL in a variety of species.…”