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*

Vasopressin, angiotensin II (AngII), and aldosterone are essential hormones in the regulation of body fluid homeostatsis. We examined the effects of AngII or aldosterone on the regulation of body water balance. We demonstrated that 1) short-term treatment with AngII in the primary cultured inner medullary collecting duct cells played a role in the regulation of AQP2 targeting to the plasma membrane through AT1 receptor activation. This potentiated the effects of dDAVP on cAMP accumulation, AQP2 phosphorylation, and AQP2 plasma membrane targeting; 2) pharmacological blockade of the AngII AT1 receptor in rats co-treated with dDAVP and dietary NaCl-restriction (to induce high plasma endogenous AngII) resulted in an increase in urine production, a decrease in urine osmolality, and blunted the dDAVP-induced upregulation of AQP2; 3) long-term aldosterone infusion in normal rats or in rats with diabetes insipidus was associated with polyuria and decreased urine concentration, accompanied by decreased apical but increased basolateral AQP2 labeling intensity in the connecting tubule and cortical collecting duct; and 4) in contrast to the effects of dDAVP and AngII, short-term aldosterone treatment does not alter the intracellular distribution of AQP2. In conclusion, angiotensin II, and aldosterone could play a role in the regulation of renal water reabsorption by changing intracellular AQP2 targeting and/or AQP2 abundance, in addition to the vasopressin.
Aldosterone* ; Angiotensin II* ; Angiotensins* ; Animals ; Aquaporin 2 ; Body Fluids ; Body Water ; Cell Membrane ; Deamino Arginine Vasopressin ; Diabetes Insipidus ; Osmolar Concentration ; Phosphorylation ; Plasma ; Polyuria ; Rats ; Up-Regulation ; Vasopressins ; Water-Electrolyte Balance

The present study was aimed at investigating the molecular regulation of the renin- angiotensin system (RAS) in two-kidney, one clip (2K1C) hypertension. The expression of renin, angiotensinogen and angiotensin II receptor genes was determined by Northern blot analysis in rats made 2K1C hypertensive for 2 or 4 weeks. The expression of renin gene was increased in the clipped kidney and decreased in the contralateral non-clipped kidney at weeks 2 and 4. The expression of angiotensinogen gene was not significantly altered at week 2, but increased at week 4 in the clipped kidney. However, it was not significantly altered in the contralateral kidney either at week 2 or 4. Nor was the expression of angiotensinogen gene significantly altered in the liver either at week 2 or 4. On the other hand, the expression of angiotensin II receptor gene was decreased at week 2, and increased at week 4 in the clipped kidney, whereas it was not significantly changed in the contralateral kidney either at week 2 or 4. In the liver, the expression of angiotensin II receptor gene was not significantly altered at week 2, but decreased at week 4. These results suggest that the components of RAS are transcriptionally regulated in 2K1C hypertension in a manner dependent on tissues and duration of hypertension.
Angiotensin II* ; Angiotensinogen* ; Angiotensins* ; Animals ; Blotting, Northern ; Hand ; Hypertension ; Kidney ; Liver ; Rats* ; Receptors, Angiotensin* ; Renin

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: 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

Mesangial cells are found to have renin and angiotensin II-AT1 receptors, but the presence of other components of the renin-angiotensin system and production of angiotensin II within the cell have not been demonstrated. The presence of the renin-angiotensin system components in the glomerular epithelial cell has not been previously reported. We studied expression of each component of the renin-angiotensin system in primary cultured rat glomerular epithelial cells and mesangial cells. We assessed mRNA expression by RT-PCR and the presence of angiotensin II by immunocytochemistry. Both cultured glomerular epithelial cells and mesangian cells expressed mRNA for components of the renin-angiotensin system such as renin, angiotensinogen and angiotensin II type 1A and 1B receptor subtypes. Immunocytochemical studies with specific antibody for angiotensin II demonstrated significant immunoreactivity in both glomerular epithelial cells and mesangian cells. These results, for the first time, provide direct evidence that both the glomerular epithelial cells and mesangian cells contain a complete renin-angiotensin system and generate angiotensin II with intracellular mechanisms. Further studies are required to define the subcellular localization of angiotensin II with electron microscopy and to elucidate the physiological importance of the intracellular reninangiotensin system.
Angiotensin II ; Angiotensinogen ; Angiotensins ; Animals ; Epithelial Cells ; Immunohistochemistry ; Mesangial Cells* ; Microscopy, Electron ; Rats* ; Renin ; Renin-Angiotensin System* ; RNA, Messenger*

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*

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