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

The present study aimed at evaluation of prophylactic efficacy and possible mechanisms of asiaticoside (AS) based standardized extract of Centella asiatica (L.) Urban leaves (INDCA) in animal models of migraine. The effects of oral and intranasal (i.n.) pretreatment of INDCA (acute and 7-days subacute) were evaluated against nitroglycerine (NTG, 10 mg·kg(-1), i.p.) and bradykinin (BK, 10 μg, intra-arterial) induced hyperalgesia in rats. Tail flick latencies (from 0 to 240 min) post-NTG treatment and the number of vocalizations post-BK treatment were recorded as a measure of hyperalgesia. Separate groups of rats for negative (Normal) and positive (sumatriptan, 42 mg·kg(-1), s.c.) controls were included. The interaction of INDCA with selective 5-HT1A, 5-HT1B, and 5-HT1D receptor antagonists (NAN-190, Isamoltane hemifumarate, and BRL-15572 respectively) against NTG-induced hyperalgesia was also evaluated. Acute and sub-acute pre-treatment of INDCA [10 and 30 mg·kg(-1) (oral) and 100 μg/rat (i.n.) showed significant anti-nociception activity, and reversal of the NTG-induced hyperalgesia and brain 5-HT concentration decline. Oral pre-treatment with INDCA (30 mg·kg(-1), 7 d) showed significant reduction in the number of vocalization. The anti-nociceptive effects of INDCA were blocked by 5-HT1A and 5-HT1B but not 5-HT1D receptor antagonists. In conclusion, INDCA demonstrated promising anti-nociceptive effects in animal models of migraine, probably through 5-HT1A/1B medicated action.
Administration, Intranasal ; Administration, Oral ; Animals ; Bradykinin ; Female ; Hyperalgesia ; chemically induced ; prevention & control ; Male ; Migraine Disorders ; chemically induced ; prevention & control ; Models, Animal ; Nitroglycerin ; Nociception ; drug effects ; Plant Leaves ; chemistry ; Pre-Exposure Prophylaxis ; Rats ; Rats, Wistar ; Reaction Time ; Receptors, Serotonin, 5-HT1 ; drug effects ; Serotonin 5-HT1 Receptor Antagonists ; metabolism ; Tail ; physiology ; Triterpenes ; administration & dosage ; pharmacology

OBJECTIVETo explore Effects of marine collagen peptides (MCPs) on markers of metablic nuclear receptors, i.e peroxisome proliferator-activated receptor (PPARs), liver X receptor (LXRs) and farnesoid X receptor (FXRs) in type 2 diabetic patients with/without hypertension. METHOD Study population consisted of 200 type 2 diabetic patients with/without hypertension and 50 healthy subjects, all of whom were randomly assigned to MCPs-treated diabetics (n = 50), placebo-treated diabetics (n = 50), MCPs-treated diabetics with hypertension (n=50), placebo-treated diabetics with hypertension (n = 50), and healthy controls (n = 50). MCPs or placebo (water-soluble starch) were given daily before breakfast and bedtime over three months. Levels of free fatty acid, cytochrome P450, leptin, resistin, adiponectin, bradykinin, NO, and Prostacyclin were determined before intervention, and 1.5 months, and 3 months after intervention. Hypoglycemia and the endpoint events during the study were recorded and compared among the study groups.

RESULTAt the end of the study period, MCPs-treated patients showed marked improvement compared with patients receiving placebo. The protection exerted by MCPs seemed more profound in diabetics than in diabetics with hypertension. In particular, after MCPs intervention, levels of free fatty acid, hs-CRP, resistin, Prostacyclin decreased significantly in diabetics and tended to decrease in diabetic and hypertensive patients whereas levels of cytochrome P450, leptin, NO tended to decrease in diabetics with/without hypertension. Meanwhile, levels of adiponectin and bradykinin rose markedly in diabetics following MCPs administration.

CONCLUSIONMCPs could offer protection against diabetes and hypertension by affecting levels of molecules involved in diabetic and hypertensive pathogenesis. Regulation on metabolic nuclear receptors by MCPs may be the possible underlying mechanism for its observed effects in the study. Further study into its action may shed light on development of new drugs based on bioactive peptides from marine sources.

Adipokines ; blood ; Aged ; Biomarkers ; blood ; Bradykinin ; blood ; C-Reactive Protein ; metabolism ; Collagen ; therapeutic use ; Cytochrome P-450 Enzyme System ; blood ; Diabetes Mellitus, Type 2 ; blood ; complications ; drug therapy ; Epoprostenol ; blood ; Fatty Acids, Nonesterified ; blood ; Female ; Humans ; Hypertension ; blood ; complications ; drug therapy ; Male ; Marine Biology ; Middle Aged ; Nitric Oxide ; blood ; Peptides ; therapeutic use ; Prospective Studies ; Receptors, Cytoplasmic and Nuclear ; metabolism

Injury or inflammation induces release of a range of inflammatory mediators. Bradykinin is one of the most important inflammatory mediators and plays a crucial role in mediating inflammatory pain. It is well known that multiple ion channels located in the nociceptors participate in pain sensation. Recent studies demonstrate an important role of bradykinin in regulating the function and expression of pain-related ion channels. This paper summarizes the recent advances in the understanding of the role of bradykinin in modulation of the channels and discusses future possibilities in the treatment of inflammatory pain.
Acid Sensing Ion Channels ; Animals ; Bradykinin ; pharmacology ; physiology ; Humans ; Inflammation ; complications ; Inflammation Mediators ; pharmacology ; physiology ; Ion Channels ; KCNQ Potassium Channels ; metabolism ; physiology ; Nerve Tissue Proteins ; metabolism ; Pain ; etiology ; metabolism ; physiopathology ; Receptors, AMPA ; metabolism ; Receptors, N-Methyl-D-Aspartate ; metabolism ; Receptors, Purinergic P2X3 ; metabolism ; Sodium Channels ; metabolism ; TRPA1 Cation Channel ; TRPV Cation Channels ; metabolism ; physiology ; Transient Receptor Potential Channels ; metabolism ; physiology

BACKGROUNDBradykinin (BK) acts mainly on two receptor subtypes: B(1) and B(2), and activation of B(2) receptor mediates the most well-known cardioprotective effects of angiotensin converting enzyme inhibitors (ACEi), however, the role that B(1) receptor plays in ACEi has not been fully defined. We examined the role of B(1) receptor in the inhibitory effect of ACE inhibitor captopril on rat cardiomyocyte hypertrophy and cardiac fibroblast proliferation induced by angiotensin II (Ang II) and explored its possible mechanism.

METHODSNeonatal cardiomyocytes and cardiac fibroblasts (CFs) were randomly treated with Ang II, captopril, B(2) receptor antagonist (HOE-140) and B(1) receptor antagonist (des-Arg(10), Leu(9)-kallidin) alone or in combination. Flow cytometry was used to evaluate cell cycle, size and protein content. Nitric oxide (NO) and intracellular cyclic guanosine monophosphate (cGMP) level were measured by colorimetry and radioimmunoassay.

RESULTSAfter the CFs and cardiomyocytes were incubated with 0.1 micromol/L Ang II for 48 hours, the percentage of CFs in the S stage, cardiomyocytes size and protein content significantly increased (both P < 0.01 vs control), and these increases were inhibited by 10 micromol/L captopril. However, NO and cGMP levels were significantly higher than that with Ang II alone (both P < 0.01). 1 micromol/L HOE-140 or 0.1 micromol/L des-Arg(10), Leu(9)-kallidin attenuated the effects of captopril, which was blunted further by blockade of both B(1) and B(2) receptors.

CONCLUSIONSActing via B(2) receptor, BK contributes to the antihypertrophic and antiproliferative effects of captopril on cardiomyocytes and CFs. In the absence of B(2) receptor, B(1) receptor may act a compensatory mechanism for the B(2) receptor and contribute to the inhibition of cardiomyocyte hypertrophy and CFs proliferation by captopril. NO and cGMP play an important role in the effect of B(1) receptor.

Angiotensin-Converting Enzyme Inhibitors ; pharmacology ; Animals ; Animals, Newborn ; Captopril ; pharmacology ; Cardiomegaly ; prevention & control ; Cell Proliferation ; drug effects ; Cell Size ; drug effects ; Cyclic GMP ; analysis ; DNA ; biosynthesis ; Fibroblasts ; drug effects ; physiology ; Myocytes, Cardiac ; drug effects ; pathology ; Nitric Oxide ; analysis ; Rats ; Rats, Sprague-Dawley ; Receptor, Bradykinin B1 ; physiology

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

OBJECTIVETo study the expression of the kallikreins-kinins system in the corpus cavernosum of rats.

METHODSThe expression of tissue kallikrein I and kinin B2 receptor gene in the corpus cavernosum and heart of adult rats was detected by reverse transcription polymerase chain reaction (RT-PCR).

RESULTSThe tissue kallikrein I and kinin B2 receptor were detected in the corpus cavernosum as well as in the heart of the rats and the contents were similar.

CONCLUSIONA kallikreins-kinins system exists in the corpus cavernosum of rats, and the content is rich, almost similar to that in the heart.

Animals ; Male ; Myocardium ; metabolism ; Penis ; metabolism ; RNA, Messenger ; genetics ; Rats ; Rats, Sprague-Dawley ; Receptor, Bradykinin B2 ; biosynthesis ; genetics ; Reverse Transcriptase Polymerase Chain Reaction ; Tissue Kallikreins ; biosynthesis ; genetics

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*

OBJECTIVE: To find out wheather the substance P takes part in the pain mediating system of uterus, and to ascertain the role of substance P in the hypersensitivity of hypogastric nerve to bradykinin during the uterine inflammation. METHODS: The uterus has two sensory innervations, which are the hypogastric nerve and the pelvic nerve. Since the hypogastric nerve is known to show increased sensitivity to bradykinin, a pain mediator, when the uterus is in inflammatory state, the hypogastric nerve recording was done for electrophysiological study of uterine pain-mediating mechanism in female SD rats (200-250 g). NK1 receptor antagonist (L-703,606) was injected through uterine artery before injecting bradykinin while uterus was under inflammation. RESULTS: The NK-1 receptor antagonist (L-703,606) decreased the spontaneous nerve impulse during inflammation, and it also decreased the hypersensitivity of the hypogastric nerve to bradykinin during the uterine inflammation. CONCLUSION: Substance P mediates the pain sense of hypogastric nerve, and it also plays a role in increased sensitivity of hypogastric nerve to bradykinin while uterus is in inflammatory state.
Action Potentials ; Animals ; Bradykinin* ; Female ; Humans ; Hypersensitivity ; Inflammation ; Mustard Plant* ; Negotiating ; Rats* ; Receptors, Neurokinin-1* ; Substance P ; Uterine Artery ; Uterus*

Angioedema is a non-pitting edema that occurs in the skin and mucus membranes. It is known that major etiologies include hereditary deficiency of C1 esterase inhibitor, temperature extreme, trauma, food sensitivity, and medications such as penicillin, aspirin, NSAIDS and ACE inhibitors. ACE inhibitors are blocking the conversion of angiotensin I to angiotensin II, a potent vasoconstrictor, and increasing local levels of bradykinin, a potent vasodilator. This increased bradykinin has been theorized to cause angioedema and cough in patients on ACE inhibitors. However, there has been very few causes of angioedema induced by angiotensin II receptor blocker. This is the first report of a patient presenting angioedema induced by losartan -angiotensin II receptor blocker- in this century.
Angioedema* ; Angiotensin I ; Angiotensin II ; Angiotensin-Converting Enzyme Inhibitors ; Anti-Inflammatory Agents, Non-Steroidal ; Aspirin ; Bradykinin ; Cough ; Edema ; Hereditary Angioedema Types I and II ; Humans ; Losartan* ; Membranes ; Mucus ; Penicillins ; Receptors, Angiotensin ; Skin