Captopril can have nephrotoxic effects, which are largely attributed to accumulated renin and "escaped" angiotensin II (Ang II). Here we test whether angiotensin converting enzyme-1 (ACE1) inhibition damages kidneys via alteration of renal afferent arteriolar responses to Ang II and inflammatory signaling. C57Bl/6 mice were given vehicle or captopril (60 mg/kg per day) for four weeks. Hypertension was obtained by minipump supplying Ang II (400 ng/kg per min) during the second 2 weeks. We assessed kidney histology by periodic acid-Schiff (PAS) and Masson staining, glomerular filtration rate (GFR) by FITC-labeled inulin clearance, and responses to Ang II assessed in afferent arterioles in vitro. Moreover, arteriolar H₂O₂ and catalase, plasma renin were assayed by commercial kits, and mRNAs of renin receptor, transforming growth factor-β (TGF-β) and cyclooxygenase-2 (COX-2) in the renal cortex, mRNAs of angiotensin receptor-1 (AT₁R) and AT₂R in the preglomerular arterioles were detected by RT-qPCR. The results showed that, compared to vehicle, mice given captopril showed lowered blood pressure, reduced GFR, increased plasma renin, renal interstitial fibrosis and tubular epithelial vacuolar degeneration, increased expression of mRNAs of renal TGF-β and COX-2, decreased production of H₂O₂ and increased catalase activity in preglomerular arterioles and enhanced afferent arteriolar Ang II contractions. The latter were blunted by incubation with H₂O₂. The mRNAs of renal microvascular AT₁R and AT₂R remained unaffected by captopril. Ang II-infused mice showed increased blood pressure and reduced afferent arteriolar Ang II responses. Administration of captopril to the Ang II-infused mice normalized blood pressure, but not arteriolar Ang II responses. We conclude that inhibition of ACE1 enhances renal microvascular reactivity to Ang II and may enhance important inflammatory pathways.
Angiotensin II/pharmacology* ; Animals ; Arterioles/metabolism* ; Captopril/pharmacology* ; Hydrogen Peroxide/pharmacology* ; Kidney ; Mice

AIMTo establish a method for determinate of the inhibitory activity of angiotensin-converting enzyme inhibitor captopril by high performance capillary electrophoresis.

METHODSThe characteristic absorptive wavelength of hippuric acid determined by ultraviolet spectrophotometer is 228 nm. The method employed a melted capillary column, 50 mmol.L-1 phosphoric acid (pH 8.3) buffer solution, inject pressure 4.8 kPa, inject time 3 s, separation voltage 20 kV and detection wavelength 228 nm.

RESULTSThe reactant and resultant was separated completed within 7 min. IC50 of captopril was 0.019 mumol.L-1. Captopril is a competitive inhibitor, which was proved by enzyme reaction dynamics.

CONCLUSIONThe method was shown to be accurate, simple and rapid and can be used for determination of the inhibitory activity of captopril.

Angiotensin-Converting Enzyme Inhibitors ; pharmacology ; Captopril ; pharmacology ; Electrophoresis, Capillary ; methods ; Hippurates ; analysis ; Peptidyl-Dipeptidase A ; metabolism

OBJECTIVE: To investigate the correlation between the carotid artery plaque and the change of plasma aldosterone level related indexes during captopril challenge test. METHODS: The patients with hypertension were enrolled as research objects and the captopril challenge test were carried out when they were hospitalized to screen the cause of hypertension. There were intact carotid artery duplex ultrasonography diagnostic data in them (83 cases). They were divided into the plaque group(57 cases) with carotid artery plaque and no plaque group( 26 cases) without carotid artery plaque according to the carotid artery duplex ultrasonography diagnostic data. The correlation between the carotid artery plaque and the changes of aldosterone concentration, renin activity and aldosterone to renin activity ratio(ARR) in two groups were analyzed. RESULTS: The detection rate of carotid artery plaque was 68.67%. Compare with no plaque group, the patients in plaque group were elder and the level of apolipoprotein A1,(APOA1) was lower (all P＜0.05). The ARR difference value before and after captopril challenge test was lower ( P＜0.05).The aldosterone difference value and the renin activity difference value before and after captopril challenge test were higher in plaque group (all P＜0.05).The aldosterone difference value and the renin activity difference value were positive in plaque group and were negative in no plaque group. The difference value of the ARR was negative in plaque group and was positive in no plaque group. Logistic regression analysis showed that the age, the difference value of ARR and the aldosterone before and after captopril challenge test could be associated independently with carotid artery plaque occurrence after excluding gender difference and other factors. CONCLUSION The detection rate of carotid artery plaque was high among hospitalized patients with hypertension, the difference value of ARR and the aldosterone before and after captopril challenge test could be associated independently with carotid artery plaque occurrence.
Aldosterone ; blood ; Angiotensin-Converting Enzyme Inhibitors ; pharmacology ; Captopril ; pharmacology ; Carotid Stenosis ; drug therapy ; Humans ; Hypertension ; drug therapy ; Inpatients ; Renin

Interleukin (IL)-6 is an autocrine growth factor for mesangial cells. It is not known whether high glucose influences IL-6 production in mesangial cells. Angiotensin II (AGII) is involved in the progression of renal diseases including diabetic nephropathy. Therefore, we evaluated the effects of high glucose in concert with AGII on IL-6 production in human mesangial cells and the modulation by blocking AGII. After 48 hr of culture, IL-6 mRNA expression was analyzed by reverse transcription and polymerase chain reaction (PCR). Quantitative determination of IL-6 concentrations in the culture supernatants of mesangial cells was performed using a sandwich enzyme immunoassay kit. Incubation of mesangial cells with high glucose (450 mg/dL) reduced the ratio of PCR products for IL-6 to beta-actin on densitometric results, while AGII (10(-7)M) increased it. The IL-6 secretion in the supernatant was also increased by AGII and decreased by high glucose. The IL-6 mRNA expression and IL-6 secretion in combination of high glucose and AGII were higher than those in high glucose and similar with those in control media. The addition of losartan (10(-6)M) or captopril (10(-6)M) to high glucose had no additional effects on IL-6 production. These results suggest that whereas AGII increases IL-6 production, high glucose decreases it. The IL-6 production of mesangial cells in diabetic milieu may be complicated and depend on the local effects of high glucose and/or AGII.
Angiotensin II/*pharmacology ; Captopril/pharmacology ; Cells, Cultured ; Gene Expression/drug effects ; Glomerular Mesangium/cytology/*metabolism ; Glucose/*pharmacology ; Humans ; Interleukin-6/*biosynthesis/genetics/secretion ; Losartan/pharmacology

A 49-year-old man with liver cirrhosis and hypertension was found to have hyperkalemia out of a degree of renal insufficiency and metabolic acidosis with low to normal anion gap, aggravated by volume contraction with diarrhea and medications (captopril, spironolactone and atenolol) interfering with potassium homeostasis. Plasma renin activity and serum aldosterone levels of this patient on a regular diet after discontinuation of medications were very low compared to those of five other cirrhotic patients with normokalemia as controls. Also, the renin-aldosterone stimulation testing on this patient performed by sodium restricted diet and furosemide, upright position and by angiotensin converting enzyme inhibition (captopril, 50 mg) showed the blunted renin and aldosterone responses to each of these stimuli, almost no changes from baseline renin and aldosterone levels, it was concluded that the underlying defect responsible for hyperkalemia in this case was hyporeninemic hypoaldosteronism and this was aggravated by other factors or drugs affecting potassium homeostasis.
Aldosterone/blood ; Captopril/pharmacology ; Furosemide/pharmacology ; Humans ; Hyperkalemia/*etiology ; Hypertension/*complications ; Hypoaldosteronism/*complications ; Liver Cirrhosis/*complications ; Male ; Middle Aged ; Renin/blood

OBJECTIVETo determine the effects of captopril on human sperm motility in vitro.

METHODSSperm specimens were aseptically obtained by masturbation and prepared by Percoll gradient-centrifugation technique to produce a spermatozoa suspension of high motility from 12 healthy fertile men. The spermatozoa suspension were incubated with captopril at 1:9 ratio of volume at 37 degrees C in vitro, which was administrated at three different concentrations. Measurements were carried out within 5 minutes for all specimens including VAP, VSL, VCL, STR, ALH and progressive motility.

RESULTSWithin 5 minutes, three different concentrations of captopril could change the human spermatozoa motility and forward motile sperm percentage, but captopril did not decrease the other motility parameters, including VSL, VCL and VAP etc. The high concentration group could decrease the VCL more than those of the other two groups and it seemed that the velocity parameters of the middle concentration group were higher than those of the other two groups, but there were no significant difference statistically.

CONCLUSIONIt suggests that captopril can decrease the human spermatozoa motility and forward motile sperm percentage, but it can not directly affect the spermatozoa velocity in vitro.

Adult ; Angiotensin-Converting Enzyme Inhibitors ; pharmacology ; Captopril ; pharmacology ; Cells, Cultured ; Dose-Response Relationship, Drug ; Humans ; Male ; Sperm Motility ; drug effects ; Spermatozoa ; cytology ; drug effects

This study inquired about the role of tumor suppressor PTEN in the arterial remodeling of Ang II induced hypertension. The expression of PTEN of aorta was examined in the aortic-constricted hypertensive rats (hypertension group), in the aortic-constricted hypertensive rats treated with captopril(hypertension and captopril group), and in the rats having undergone sham operation (control group). At day 28 after surgery, the aortas were collected from the groups. The expression of PTEN mRNA was detected by RT-PCR. The expression and location of PTEN protein were determined by immunohistochemistry. The results showed that the expression of PTEN in aorta of the hypertension group was significantly lower than that of the hypertension and captopril group, and similarly lower than that of the control group. The intensity of PTEN-positive immunohistochemical production in aorta of the hypertension group was weaker than that of the hypertension and captopril group, and likewise, it was weaker than the control. PTEN-positive immunohistochemical production was located in VSMC of aorta. The findings indicated that the expression of PTEN is reduced in hypertensive aorta, that the reduced PTEN experession can be reversed by captopril treatment, that AngII and the increased mechanical strain may participate in regulating expression of PTEN, and that PTEN may play a role in the arterial remodeling induced by hypertension.
Angiotensin-Converting Enzyme Inhibitors ; pharmacology ; Animals ; Aorta, Abdominal ; metabolism ; Captopril ; pharmacology ; Constriction ; Genes, Tumor Suppressor ; Hypertension ; etiology ; metabolism ; Male ; PTEN Phosphohydrolase ; biosynthesis ; genetics ; Rats ; Rats, Sprague-Dawley

AIMTo investigate the role of tumor suppressor PTEN in cardiac hypertrophy, the expression of PTEN mRNA in left ventricle of abdominal aorta constricted-induced cardiac hypertrophic rats which treated with and without captopril was analyzed.

METHODSSD rats were divided into control group, hypertrophy group and captopril group. The expression of PTEN mRNA in left ventricle was detected by RT-PCR in different groups in 4 weeks after operation.

RESULTS(1) Compared with control group, the expression of PTEN mRNA in left ventricle of hypertrophy group was reduced. (2) Compared with hypertrophy group, the expression of PTEN mRNA in left ventricle of captopril group was upregulated, which were similar to that of control group.

CONCLUSIONPTEN maybe plays a negative regulation role in the process of cardiac hypertrophy, and the role of PTEN is closely relative with renin-angiotensin system.

Angiotensin-Converting Enzyme Inhibitors ; pharmacology ; Animals ; Captopril ; pharmacology ; Cardiomegaly ; metabolism ; pathology ; Male ; PTEN Phosphohydrolase ; metabolism ; RNA, Messenger ; genetics ; Rats ; Rats, Sprague-Dawley

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 effect of captopril on the nervous function in rabbits exposed to vibration.

METHODSRabbits were divided into vibration group, intervention group, and control group. Vibration group and intervention group were exposed to (tested by) vibration. Captopril was given to intervention group from the 11th day of vibration exposure. Somatosensory evoked potential (SEP) and motor nervous conduction function (MCF) were measured and analyzed in each group before and after vibration exposure.

RESULTSThe latent periods of N1, P1 and N2 of SEP in vibration group after vibration exposure were (30.76 +/- 4.26), (41.91 +/- 6.67), and (45.29 +/- 5.81) ms respectively, and in intervention group after vibration exposure were (27.00 +/- 3.04), (35.07 +/- 4.20) and (41.15 +/- 3.19) ms respectively. Compared with intervention group before and after exposure, and control group, the latent periods of each wave of SEP were delayed significantly (P < 0.05). The nervous conduction velocity, the distant wave amplitude, and the distant potential period of sciatic nerve in vibration group after vibration exposure were significantly different from those in intervention group [(35.69 +/- 4.37) m/s, (1.55 +/- 0.73) microV, (8.16 +/- 0.71) ms respectively vs (52.20 +/- 5.13) m/s, (2.89 +/- 0.36) microV, (7.26 +/- 0.77) ms respectively (P < 0.01)].

CONCLUSIONCaptopril may improve the impairment of nervous functions to a certain degree in rabbits exposed to vibration.

Animals ; Captopril ; pharmacology ; Evoked Potentials, Somatosensory ; drug effects ; Female ; Male ; Neural Conduction ; drug effects ; Rabbits ; Sciatic Nerve ; drug effects ; physiology ; Vibration ; adverse effects