In an attempt to treat the cold urticaria, a new bradykinin inhibitor, homoclomin was administered orally and effective result were obtained. The urticaria was confirmed by the employing the ice cube test on the patient and the positive reaction was appeared generally 10 sec. to 15 min. after application of ice cube on the forearm. After oral administration for 3 days (40mg/day) clinical symptoms were relieved temporarily and weakly positive or negative reaction observed in repeated ice cube test.
Administration, Oral ; Bradykinin ; Forearm ; Humans ; Ice* ; Urticaria*

Interstitial Cells of Cajal (ICC) are pacemaker cells that generates slow waves and drive spontaneous mechanical contractions of gastrointestinal smooth muscle. Slow waves are generated the periodic activation of spontaneous inward currents (pacemaker currents). We studied the modulation of pacemaker activities by bradykinin (10-8 M) in cultured ICC with the whole cell patch-clamp technique, and the localization of bradykinin-2 receptor-immunoreactivity using double labelling immunohistochemistry in the murine small intestine. Externally applied bradykinin produced membrane depolarization in current-clamping mode. At a -70 mV of holding potential bradykinin increased tonic inward pacemaker currents. Double labelling with bradykinin-2 receptor and and c-kit was shown that ICC expressed the bradykinin-2 receptor-immunoreactivity. These results suggest that bradykinin modulates electrical activities of ICC via bradykinin-2 receptor, which may regulate gastrointestinal motility.
Animals ; Bradykinin* ; Gastrointestinal Motility ; Immunohistochemistry ; Interstitial Cells of Cajal* ; Intestine, Small* ; Membranes ; Mice* ; Muscle, Smooth ; Patch-Clamp Techniques ; Receptors, Bradykinin*

OBJECTIVETo study the expression of bradykinin and its receptors B1R and B2R in the kidney immune injury in trichloroethylene-sensitized mouse and discuss the pathogenesis of Dermatitis Medicamentosa-like of TCE (ODMLT).

METHODSOn the first days, intradermal injection by 50% TCE and the amount of FCA mixture 100 µl for initial sensitization; on 4, 7, 10 days, painted abdominal skin by 100 µl 50% TCE for three sensitization, on 17, 19 days, painted on the back skin by 100 µl 30% TCE for initial excitation and the last challenge; 24 h before each challenge, PKSI-527+TCE group received intraperitoneal injection by inhibitor PKSI-527 (50 mg/kg); solvent control group treat without TCE and sensitization and excitation reagent the same proportion of olive oil and acetone mixture, blank control group without any treatment. Before killing the mouse, renal weight and body weight were recorded. The renals and plasma were separated at 24 h, 48 h, 72 h and 7 d after the last challenge and observed pathological of the renals. Expression of B1R and B2R in renal were examined by immunofluorescence technique. Plasma were examined by ELISA for BK.

RESULTSThe renal pathological examination revealed the apparent damage of TCE sensitized mice which compared to solvent control group showed obvious cellular infiltration, vacuolar degeneration of renal tubular epithelial cells. The renal damage of PKSI-527+TCE-sensitized groups which compared to the corresponding point of TCE-sensitized groups showed significantly reduced. The expression of BK in 24 h, 48 h and 72 h TCE-sensitized groups were significant higher than solvent control group and related TCE non-sensitized groups (P < 0.05) and 72 h point compared to the corresponding point of PKSI-527+TCE group was also increased, the difference was statistically significant (P < 0.05). The expression levels of B1R and B2R in the kidney in 24 h, 48 h, 72 h and 7 d TCE-sensitized groups were obviously higher than solvent control group and related TCE non-sensitized groups. The expression levels of B1R and B2R in the kidney in the four point of PKSI-527+TCE sensitized group were relatively lower than the corresponding point of TCE sensitized group.

CONCLUSIONKKS activation may involved in the renal immune injury of trichloroethylene-sensitized mouse and the expression change of bradykinin and its receptors B1R and B2R which may play an important role in the process.

Administration, Cutaneous ; Animals ; Bradykinin ; metabolism ; Kidney ; drug effects ; metabolism ; pathology ; Mice ; Phenylalanine ; analogs & derivatives ; Receptor, Bradykinin B1 ; metabolism ; Receptor, Bradykinin B2 ; metabolism ; Solvents ; Tranexamic Acid ; analogs & derivatives ; Trichloroethylene ; toxicity

Animals ; Apoptosis ; Bradykinin ; metabolism ; Bradykinin Receptor Antagonists ; Ischemia ; metabolism ; Ischemic Preconditioning ; Muscle, Skeletal ; blood supply ; metabolism ; pathology ; Myocardial Infarction ; metabolism ; Myocardium ; pathology ; Swine ; Swine, Miniature

AIMTo investigate the role and mechanism of the bradykinin(BK) B1 receptor in the antiproliferative effects of the angiotensin-converting enzyme inhibitor (ACEI) captopril on rat cardiac fibroblasts (CFs) treated with angiotensin II (Ang II).

METHODSNeonatal rat cardiac fibroblasts were randomly treated with Ang II, captopril, B2 receptor antagonist (icatibant) or B1 receptor antagonist (des-Arg10, Leu9-kallidin). Thiazolyl blue (MTT) and flow cytometry (FCM) were used to evaluate cell number and cell cycle, respectively. Nitric oxide (NO) and intracellular cGMP level were measured by colorimetry and radioimmunoassay.

RESULTSAfter incubating the fibroblasts with 10(-7) mol/L Ang II for 48 hours, the percentage of CFs in the S stage and the value of MTT A490 nm were significantly increased (P < 0.01 vs control), and this increase was inhibited by 10(-5) mol/L captopril; however, NO and cGMP level were significantly higher than with Ang II alone (P < 0.01). 10(-5) mol/L icatibant attenuated the effects of captopril, which were blunted further by dual blockade of both B1 and B12.

CONCLUSIONActing via the B2 receptor, BK contributes to the antiproliferative effects of ACEI on CFs. In the absence of the B2 receptor, the B1 receptor may assume some of the functions of the B2 receptor and contribute to inhibition of CFs proliferation by ACEI.

Animals ; Bradykinin B1 Receptor Antagonists ; pharmacology ; Captopril ; pharmacology ; Cell Proliferation ; drug effects ; Heart Ventricles ; Myocytes, Cardiac ; cytology ; Rats ; Rats, Sprague-Dawley ; Receptor, Bradykinin B1 ; metabolism

Angiotensin-converting enzyme (ACE), a dipeptidyl carboxypeptidase, hydrolyzes angiotensin I to the active angiotensin g and also inactivates bradykinin. Activity of ACE was first identified in plasrna by Skeggs et al in 1956. In 1975 Lieberman first reported elevation of serum ACE level in patients with active sarcoidosis and suggested clinical application of the assay to confirm a diagnosis of sarcoidosis and to serve as a guide for therapy. The author studied the serurn ACE levels in 21 syphilitic patients (11 men, 10 women) who showed positive responses in both VDRL and TPHA tests and 20 normal healthy controls (7 men, 13 women) by the spectrophotometric method described by Lieberrnan who modified Cushman and Cheungs method. Comparative studies of ACE levels in syphilitic group with normal control group and relationship among the age, sex and treatment were also conducted. The results were summarized as follows : Ages of the syphilitic patients and normal healthy control group ranged from 18 to 51 years (27 1+-8 98 years) and from 14 to 49 years (28 4+9 08 years) respectively. The mean serum ACE level in syphilitic patients was ll 33+-3 25 p/ml, which was significantly higher than that of normal healthy control group, 6 39+-2 RR p/ml, (p<0001) Of the 21 syphilitic patients, 15(71 4%) had ACE activity higher than the upper limit of normal (mean+1SD). There was no significant correlation between age and serum ACE level. -countinue-
Angiotensin I ; Angiotensins* ; Bradykinin ; Diagnosis ; Humans ; Male ; Peptidyl-Dipeptidase A* ; Sarcoidosis ; Syphilis*

BACKGROUND AND OBJECTIVES: Angiotensin -converting enzyme (ACE) inactivates bradykinin, substance P, and neurokinin A, which are thought to play important roles in the pathogenesis of inflammatory diseases. An insertion/deletion (I/D) poly - morphism in the ACE gene was reported to be associated with atopy in a Czech population. MATERIALS AND METHODS: Using the polymerase chain reaction, we investigated the frequencies of the genotypes and alleles of the ACE gene in 137 patients with allergic rhinitis and 498 healthy control subjects. RESULTS: There was no difference in the frequencies of the genotypes in the controls and patients with allergic rhinitis (p>0.05). The D allele was more frequent in patients with allergic rhinitis, but the difference was not statistically significant (p>0.05). CONCLUSION: Our results indicate that I/D polymorphism in the ACE gene is not related to susceptibility to allergic rhinitis in the Korean population.
Alleles ; Angiotensins ; Bradykinin ; Genotype ; Humans ; Neurokinin A ; Polymerase Chain Reaction ; Rhinitis* ; Substance P

BACKGROUND: Using the urinary bladder as a model, neurophysiological studies of visceral primary afferents supplying inflamed tissue have been studied. In this study we have examined the response of the hypogastric afferents supplying the urinary bladder of the cat to intra-arterially injected algesic chemicals after experimental inflammation. METHODS: Twenty units were recorded from the strands of hypogastric nerve. Once a unit was found, the conduction velocity was determined by extracellular recording of single fiber. When the response of the unit excited by mechanical stimuli was found, chemical stimuli were applied by intra-arterial injection of algesic chemicals (bradykinin, KCl). And then, irritant chemical, 3% mustard oil injected into the urinary bladder for the induction of an experimental inflammation. After removal of the irritant and with the empty bladder, the response of the afferent unit to chemical stimuli by intra-arterially injected bradykinin and KCl were studied again. RESULTS: All units were found to be A delta fibers and responded to both mechanical and chemical stimuli. After experimental inflammation, the basal tone and spontaneous contraction of the urinary bladder were increased and spontaneous nerve activity of the hypogastric afferents appeared. Bladder contraction and nerve activity to intra-arterially injected bradykinin decreased more than those of controls before inflammation. The ratio of nerve activity to the bladder contraction after experimental inflammation was increased. CONCLUSIONS: The hypogastric afferents were sensitized after inflammation, which showed increased nerve response to intra-arterially injected bradykinin comparing to the contraction response of the urinary bladder.
Animals ; Bradykinin ; Cats ; Cystitis* ; Inflammation ; Injections, Intra-Arterial ; Mustard Plant ; Sensory Receptor Cells* ; Urinary Bladder*

Nitric oxide (NO) is known to act as an important neural mediator of penile erection. However, the degree of penile erection related to the concentration of NO released from corpus cavernosum has not been known yet. The present study was undertaken to correlate the degree of relaxation of the corpus cavernosum with concentration of NO by treatment of various NO releasing agents. Isometric tension of the rabbit cavernous strips was measured by polygraph system. The concentration of NO released from the same strips was simultaneously measured using an electrochemical method (Iso NO meter), which allows to detect change of NO gas level in perfusate of the organ bath. The cumulative additions of endothelial dependent agents, both acetylcholine and bradykinin at concentration from 0.00000001 to 0.0001M relaxed the cavernous strips precontracted by 0.000001M phenylephrine in concentration-dependent manner, which were highly correlated with the concentration of NO (38.9 +/- 15.2 nM at 0.00000001M - 74.5 +/- 18.4 nM at 0.0001M of acetylcholine; 30.2 +/- 5.8 nM at 0.00000001M - 90.5 +/- 10.2 at 0.0001M of bradykinin) released from the same strips, Furthermore, 3-[(3-cholamido propyl)]-l-propane sulfonate (CHAPS), a deendothelial agent, markedly suppressed both acetylcholine or bradykinin-induced cavernous relaxation and abolished NO release. In contrast, endothelial independent agent such as sodium nitroprusside (SNP), N-ethoxycarbonyl-3-morpholino-sydonimine (SIN-l) and s-nitroso-N-acetylpenicillamine (SNAP) at concentration from 0.00000001 to 0.001M relaxed the cavernous strips in` concentration dependent manner, without altering the basal concentration of NO in perfusate. From these results, it appears that the degree of cavernous relaxation induced by acetylcholine or bradykinin is highly correlated with the concentration of NO released from the cavernous endothelium. Furthermore, the direct electrochemical measurement of NO concentration in perfusate may be useful for further NO research in association with penile erection.
Acetylcholine ; Baths ; Bradykinin ; Endothelium ; Male ; Nitric Oxide* ; Nitroprusside ; Penile Erection ; Phenylephrine ; Relaxation* ; S-Nitroso-N-Acetylpenicillamine

In spite many evidences has supported the cardioprotective effect of bradykinin, its direct effects at the cell level are still under question. We investigated the both effects of bradykinin (BK) on Ca2+-related ionic currents using whole cell voltage clamp technique in rabbit cardiomyocytes and on the intracellular Ca2+ transient using calcium sensitive fluorescence dye, indo-1AM. Simultaneously with recording intracellular Ca2+ transients, cell contractility was estimated from the changes in length of the electrical stimulated rat cardiac myocytes. L-type Ca2+ current decreased by bradykinin at the entire voltage range. Inward tail current increased initially up to its maximum about 4 min after exposing myocytes to BK, and then gradually decreased again by further exposure to BK. This tail current decreased remarkably at washing BK off but slowly recovered ca. 20 min later. The change in cell contractility was similar to that in tail current showing initial increase followed by gradual decrease. Removal of BK brought remarkable decrease in contractility, which was recovered 15~20 min after cessation of electrical stimulation. Bradykinin increased Ca2+ transient initially but after some time Ca2+ transient also decreased coincidentally with contractility. From these results, it is suggested that bradykinin exerts directly its cardioprotective effect on the single myocytes by decreasing the intracellular Ca2+ level followed by an initial increase in Ca2+ transient.
Animals ; Bradykinin* ; Calcium* ; Electric Stimulation ; Fluorescence ; Muscle Cells ; Myocytes, Cardiac* ; Rats