PURPOSE: Angiotensin(ANG) II regulates tone of penile smooth muscle for erection. ANG III is a product converted from ANG II by aminopeptidase A. The effects of ANG III have not been clarified in the penile corpus cavernosum. The purpose of the present experiment was to determine whether the ANG III has regulatory function in the control of rabbit corpus cavernosum smooth muscle tone. MATERIALS AND METHODS: A strip of rabbit corpus cavernosum was mounted in an organ chamber to measure the isometric tension. We compared the effects of ANG III(10-7M to 10-5M), ANG II(10-8M to 10-6M) and ANG I(10-7M to 10-5M) on the contractility of the corpus cavernosum smooth muscle. RESULTS: ANG III, ANG II, and ANG I contracted corpus cavernosum smooth muscle strips dose-dependently. The contraction of smooth muscle induced by ANG III was 10 fold less by ANG II. Contractile response to ANG III was not attenuated by captopril(angiotensin converting enzyme inhibitor). Contractile response to ANG III was significantly inhibited by Dup 753 of 10-7M(type 1 specific ANG II receptor inhibitor) but not inhibited by PD 123,319 of 10-6M(type 2 specific ANG II inhibitor). CONCLUSIONS: The present results suggest that ANG III is involved in the regulation of corpus cavernosum smooth muscle tone, and contractile effect to ANG III produced via activation of type 1 ANG II (AT1) receptor. The rank order of potency of contraction was as follows, ANG II>ANG IIIANG I.
Angiotensin I* ; Angiotensin II* ; Angiotensin III* ; Angiotensins* ; Glutamyl Aminopeptidase ; Losartan ; Muscle, Smooth*

PURPOSE: To evaluate the effects of prostaglandin analogues on the corneal thickness of patients with primary open-angle glaucoma (POAG) or normal tension glaucoma (NTG). METHODS: This study included 130 eyes of 65 patients who were diagnosed with POAG or NTG. All patients were divided into two groups; one group received prostaglandin analogues, while the other group received alternative ocular hypotensive eyedrops. Corneal thickness, best corrected visual acuity, and flare in the anterior chamber were measured and compared before treatment and at least 24 months (mean: 27 months) after treatment. RESULTS: The mean decrease in corneal thickness was statistically significant in the group using prostaglandin analogues, but not in the control group. Among the various prostaglandin analogues used, travoprost and latanoprost decreased mean corneal thickness, but bimatoprost had no effect. Best corrected visual acuity, refraction power, and flare in the anterior chamber did not change significantly in either group of patients when ocular hypotensive eyedrops were used. CONCLUSIONS: Prostaglandin analogues lower intraocular pressure and decrease corneal thickness if used over a 24 months.
Amides ; Anterior Chamber ; Cloprostenol ; Eye ; Glaucoma, Open-Angle ; Humans ; Intraocular Pressure ; Low Tension Glaucoma ; Ophthalmic Solutions ; Prostaglandins F, Synthetic ; Prostaglandins, Synthetic ; Visual Acuity ; Bimatoprost ; Travoprost

Angiotensin II(A II) -a main effector molecule of renin-angiotensin system(RAS) has been known to increase blood pressure and glomerular capillary pressure, and filtration fraction which may be involved in the progressive renal injury process. The action of A II takes place mainly through AT1 receptor. RAS can be blocked by angiotensin converting enzyme inhibitor(ACEI) and recently developed A II AT1 receptor antagonist(AT1 RA). ACEI also activate kinin system, simultaneously. However, AT1 RA does not affect kinin system. The renoprotective mechanism of ACEI may be related with activation of kinin system. In order to evaluate the renoprotective mechanism of long-term ACEI(enalapril, 100mg/L in drinking water for 12 weeks) or AT1 RA treatment(losartan 300mg/L in drinking water for 12 weeks), and its effect on the cytokines and growth factor expressions of renal cortical tissue by compatitive RT-PCR, 46 5/6 nephrectomized(5/6 NPX) rats and 8 sham operated rats were included in this study. Five sixth NPX rats showed marked hypertensin, significant proteinuria and glomerulosclerosis(mean 30.5%) in 12 weeks after surgery. However, enelapril or losartan treated rats revealed significantly lower 24 hour urinary protein excretion(UProtV), systolic blood pressure(SBP), and glomerulosclerosis than those of control 5/6 NPX rats. Plasma renin activity and angiotensin II levels of 5/6 NPX untreated control rats were not significantly increased compared to sham operated rats in 12 week after surgery. Renal cortical renin gene expression of untreated 5/6 NPX rats was significantly suppressed compared to sham operated rats. Enalapril or losartan treated 5/6 NPX rats showed significantly increased renin gene expression compared to untreated 5/6 NPX rats. Renal cortical gene expressions of TGF-beta, TNF-alpha, MCP-1, IL-6, osteopontin, and endothelin-1 were significantly increased in 5/6 NPX untreated control rats compared to sham operated rats. Enalapril or losartan treated 5/6 NPX rats showed significantly less level of renal TGF-beta gene expression compared to 5/6 NPX control rats. The magnitude of SBP and UProtV were significantly positively correlated with the degree of glomeruloslerosis(p<0.001, p<0.001). With the above result, we speculate that because ACEI or AT1 RA showed similar renoprotective effect in 5/6 NPX rats, at least in part, local activation of RAS plays an important role in the progressive renal injury process of this model.
Angiotensin Amide ; Angiotensin II ; Angiotensins ; Animals ; Blood Pressure ; Capillaries ; Cytokines ; Drinking Water ; Enalapril ; Endothelin-1 ; Filtration ; Gene Expression ; Interleukin-6 ; Losartan ; Osteopontin ; Peptidyl-Dipeptidase A ; Plasma ; Proteinuria ; Rats ; Renin ; Renin-Angiotensin System* ; Transforming Growth Factor beta ; Tumor Necrosis Factor-alpha

Angiotensin II(A II) -a main effector molecule of renin-angiotensin system(RAS) has been known to increase blood pressure and glomerular capillary pressure, and filtration fraction which may be involved in the progressive renal injury process. The action of A II takes place mainly through AT1 receptor. RAS can be blocked by angiotensin converting enzyme inhibitor(ACEI) and recently developed A II AT1 receptor antagonist(AT1 RA). ACEI also activate kinin system, simultaneously. However, AT1 RA does not affect kinin system. The renoprotective mechanism of ACEI may be related with activation of kinin system. In order to evaluate the renoprotective mechanism of long-term ACEI(enalapril, 100mg/L in drinking water for 12 weeks) or AT1 RA treatment(losartan 300mg/L in drinking water for 12 weeks), and its effect on the cytokines and growth factor expressions of renal cortical tissue by compatitive RT-PCR, 46 5/6 nephrectomized(5/6 NPX) rats and 8 sham operated rats were included in this study. Five sixth NPX rats showed marked hypertensin, significant proteinuria and glomerulosclerosis(mean 30.5%) in 12 weeks after surgery. However, enelapril or losartan treated rats revealed significantly lower 24 hour urinary protein excretion(UProtV), systolic blood pressure(SBP), and glomerulosclerosis than those of control 5/6 NPX rats. Plasma renin activity and angiotensin II levels of 5/6 NPX untreated control rats were not significantly increased compared to sham operated rats in 12 week after surgery. Renal cortical renin gene expression of untreated 5/6 NPX rats was significantly suppressed compared to sham operated rats. Enalapril or losartan treated 5/6 NPX rats showed significantly increased renin gene expression compared to untreated 5/6 NPX rats. Renal cortical gene expressions of TGF-beta, TNF-alpha, MCP-1, IL-6, osteopontin, and endothelin-1 were significantly increased in 5/6 NPX untreated control rats compared to sham operated rats. Enalapril or losartan treated 5/6 NPX rats showed significantly less level of renal TGF-beta gene expression compared to 5/6 NPX control rats. The magnitude of SBP and UProtV were significantly positively correlated with the degree of glomeruloslerosis(p<0.001, p<0.001). With the above result, we speculate that because ACEI or AT1 RA showed similar renoprotective effect in 5/6 NPX rats, at least in part, local activation of RAS plays an important role in the progressive renal injury process of this model.
Angiotensin Amide ; Angiotensin II ; Angiotensins ; Animals ; Blood Pressure ; Capillaries ; Cytokines ; Drinking Water ; Enalapril ; Endothelin-1 ; Filtration ; Gene Expression ; Interleukin-6 ; Losartan ; Osteopontin ; Peptidyl-Dipeptidase A ; Plasma ; Proteinuria ; Rats ; Renin ; Renin-Angiotensin System* ; Transforming Growth Factor beta ; Tumor Necrosis Factor-alpha

BACKGROUND: The angiotensin coverting enzyme(ACE) gene(encoding kininase II, EC3.4.15.1) contains a polymorphism based on the presence(insertion [I]) or absence(deletion[D]) within an intron of a 287bp nonsense DNA domain, resulting in three genotypes(D/I) and I/I homozygotes, and I/D heterozygotes). Alu insertion is associated with lowerACE level than deletion allele(D) and it was observed that D/D individuals have twice theACE activity of I/I patients. Pregnancy induced hypertension(PIH) probably results fromdominating pressor systems owing to loss of antagonizing vasodilator autacoids. AngiotensinII is an extremely potent arteriolar vasoconstrictor. Overactivity or failure to supressresponsiveness to the increased activity of angiotensin II, which is generated by ACE,would seem to be a reasonable basis for the vasoconstriction of PIH. The aim of this studyis to evaluate the relationship between ACE genotype and PIH. METHODS: Blood sampling was taken from 39 patients with PIH. The hypertensivedisorders, confirmed at postpartum follow up, were classified as gestational hypertensionwithout proteinuria, preeclampsia(mild and severe) and eclampsia. The diagnosis ofpreeclampsia was made according to the American College of Obstetrics and Gynecology criteriaof hypertension and proteinuria(>300 mg/24 hr urine). Genomic DNA was extractedfrom blood sample. After PCR amplification of the respective fragments from intron 16 ofthe ACE gene, size fractionation and visualization by electrophoresis were performed. RESULTS: PIH group(including gestational hypertension, mild and severe preeclampsia: frequency of I allele 0.756 and D allele 0.244) had more I allele and less D allele whencompared with normal population(frequency of I allele 0.609 and D allele 0.391)(p < 0.05).And PIH group had more I/I homozygote individuals showing significant distortion fromHardy-Weinberg equilibrium of ACE genotype(p < 0.05). Moreover, severe preeclampsiagroup alon(frequency of I allele 0.759 and D allele 0.241) had more I allele and less Dallele when compared with normal population and had significantly more I/I homozygoteindividuals. CONCLUSION: As pregnancies with PIH had more ACE I allele and I/I homozygoteindividuals. PIH could be associated with I allele of the ACE gene. Considering the observedcodominant association between the D-I polymorphism and plasma ACE activity, our resultis in favor of the thesis that PIH primarily arises from defective synthsis of vasodilatingautacoids and renin-angiotensin system exerts secondary vasoconstrictive action. However,the relationship between ACE genotype and defective vasodilating mechanism during pregnancyis unknown at present.
Alleles ; Angiotensin II ; Angiotensins* ; Autacoids ; Diagnosis ; DNA ; Eclampsia ; Electrophoresis ; Female ; Follow-Up Studies ; Genotype ; Gynecology ; Homozygote ; Humans ; Hypertension ; Hypertension, Pregnancy-Induced ; Introns ; Obstetrics ; Peptidyl-Dipeptidase A ; Plasma ; Polymerase Chain Reaction ; Postpartum Period ; Pre-Eclampsia ; Pregnancy* ; Proteinuria ; Renin-Angiotensin System ; Vasoconstriction

No abstract available.
Angiotensin I ; Angiotensin II* ; Angiotensins* ; Autoradiography ; Receptors, Angiotensin* ; Renin* ; Renin-Angiotensin System*

No abstract available.
Angiotensin I ; Angiotensin II* ; Angiotensins* ; Autoradiography ; Receptors, Angiotensin* ; Renin* ; Renin-Angiotensin System*

BACKGROUND: Angiotensin converting enzyme (ACE) is heavily expressed in the lung and plays a role in the metabolism of angiotensin II, bradykinin and substance P. Nitric oxides, including those produced by endothelial nitric oxide synthase (ecNOS), may regulate vascular and airway tone in the lung and influence various aspects of airway homeostasis. They are potentially involved in the pathogenesis of asthma, but the role of ACE and ecNOS gene in bronchial asthma is not completely understood. OBJECTIVE: To examine the possible involvement of ACE and ecNOS genes in the genetic basis for bronchial asthma, we investigated the association between genetic polymorphism and bronchial asthma, and its severity. METHOD: We determined the ACE and ecNOS genotypes by the polymerase chain reaction in 160 patients with bronchial asthma and 121 healthy subjects. Severity of asthma was classified by the guideline of NHLBI/WHO workshop. RESULTS: The frequency of the ID genotypes of ACE and bb genotype of ecNOS was highest in both groups, respectively. The distribution of ACE genotypes did not differ between the two groups (p=0.27). There was a higher frequency of the bb genotype of ecNOS in the asthma group than in the control population (p=0.004). In asthmatic patients, there were no differences in the distribution of ACE and ecNOS genotypes in different severity groups (p= 0.17, 0.06). CONCLUSION: These results suggest that the polymorphism of the ecNOS gene, not ACE gene, may be associated with development of asthma. But, the severity of asthma may not be influenced by polymorphisms of the ecNOS and ACE genes.
Angiotensin II ; Angiotensins* ; Asthma* ; Bradykinin ; Education ; Genotype ; Homeostasis ; Humans ; Lung ; Metabolism ; Nitric Oxide Synthase Type III* ; Oxides ; Peptidyl-Dipeptidase A* ; Polymerase Chain Reaction ; Polymorphism, Genetic ; Substance P

Many reports represent that angiotensin II (ANG II) caused a dose dependent biphasic effects on fluid transport in the proximal tubule. However, respective roles of different signaling pathways in mediating these effects remain unsettled. The aim of the present study was to examine signaling pathways at high doses of ANG II on the Na+ uptake of primary cultured rabbit renal proximal tubule cells(PTCs) in hormonally defined serum-free medium. High concentrations of ANG II (> 10(-9) M) inhibited Na+ uptake and increased (Ca2+)i level in the PTCs. However, low concentrations of (< 10(-11) ANG II) stimulated Na+ uptake and did not affect (Ca2+)i level. 8-(N, N-diethylamino)-octyl-3,3,5- trimethoxybenzoate (TMB-8), ethylene glycol-bis(beta-amino ethyl ether)-N,N,N', N'-tetra acetic acid (EGTA), and nifedifine partially blocked the inhibitory effects of ANG II on Na+ uptake. When ANG II and bradykinin (BK) were treated together, Na+ uptake was further reduced (88.47 +/- 1.98% of that of ANG II, 81.85 +/- 1.84% of that of BK). In addition, W-7 and KN-62 blocked the ANG II-induced inhibition of Na+ uptake. Arachidonic acid reduced Na+ uptake in a dose-dependent manner. When ANG II and arachidonic acid were treated together, inhibitory effects on Na+ uptake significantly exhibited greater reduction than that of each group, respectively. When PTCs were treated by mepacrine (10(-6) M) and AACOCF, (10-5 M) for 1 hr before the addition of 10(-9) M ANG II, the inhibitory effect of ANG II was reversed. In addition, econazole (10(-6) M) blocked ANG II-induced inhibition of Na+ uptake. In conclusion, the (Ca2+)i (calcium-calmodulin-dependent kinase) and phospholipase A2 (PLA2) metabolites are involved in the inhibitory effects of ANG II on Na+ uptake in the PTCs.
Acetic Acid ; Angiotensin II* ; Angiotensins* ; Arachidonic Acid ; Bradykinin ; Econazole ; Ion Transport* ; Kidney ; Negotiating ; Phospholipases A2 ; Quinacrine

Pharmacotherapy for the treatment of heart failure has advanced considerably in recent years, and clinical trials have demonstrated the favorable long-term effects of angiotensin-converting enzyme inhibitors (ACEI) and beta-blockers on the morbidity and mortality. Although the current guidelines recommend ACEI and beta-blockers as standard therapy for heart failure, as they have demonstrated benefits in terms of mortality, only one third of patients with heart failure are receiving both classes of drug due to concern over their adverse effects. The benefit of ACEI has been attributed largely to blockade of angiotensin II production, but also to the accumulation of bradykinin. The accumulation of bradykinin however, has been implicated as contributing to adverse effects, such as a dry cough, associated with ACEI treatment, and has also been suggested to result in prejunctional norepinephine release. Recently, many clinical trials have shown that angiotensin receptor blockers (ARBs) had similar effect on the mortality and morbidity of patients with heart failure. The side effects, notably the cough, are significantly less than with ACE inhibitors. ARBs could also be recommended for patients who can not tolerate ACE inhibitors for symptomatic treatment. In combination with ACEI, ARBs may improve the symptoms of heart failure, and reduce hospitalizations due to heart failure deterioration. Whether concomitant beta-blockade negatively affects the effect of ARB will require further evaluation. In this paper, recent large clinical trials of ARBs therapy in heart failure, and the ongoing clinical trials, were reviewed for the recommendation of the optimal conditions for ARBs treatment in heart failures.
Angiotensin II* ; Angiotensin Receptor Antagonists* ; Angiotensin-Converting Enzyme Inhibitors ; Angiotensins* ; Bradykinin ; Cough ; Drug Therapy ; Estrogens, Conjugated (USP)* ; Heart ; Heart Failure* ; Hospitalization ; Humans ; Mortality ; Receptors, Angiotensin*