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The renin-angiotensin system in the kidney plays a critical role in the regulation of renal hemodynamics and sodium handling through the activation of vascular, glomerular and tubular angiotensin II type 1 (AT1) receptor-mediated signaling. We previously cloned a molecule that specifically bound to the AT1 receptor and modulated AT1 receptor signaling in vitro, which we named ATRAP (for AT1 receptor-associated protein). The purpose of this study is to analyze the renal distribution of ATRAP and to examine whether ATRAP is co-expressed with the AT1 receptor in the mouse kidney. We performed in situ hybridization, Western blot analysis, and immunohistochemistry to investigate the expression of ATRAP mRNA and protein in the mouse kidney. The results of Western blot analysis revealed the ATRAP protein to be abundantly expressed in the kidney. Employing in situ hybridization and immunohistochemistry, we found that both ATRAP mRNA and the protein were widely distributed along the renal tubules from Bowman's capsules to the inner medullary collecting ducts. ATRAP mRNA was also detected in the glomeruli, vasculature, and interstitial cells. In all tubular cells, the ATRAP protein colocalized with the AT1 receptor. Finally, we found that the dietary salt depletion significantly decreased the renal expression of ATRAP as well as AT1 receptor. These findings show ATRAP to be abundantly and broadly distributed in nephron segments where the AT1 receptor is expressed. Furthermore, this is the first report demonstrating a substantial colocalization of ATRAP and AT1 receptor in vivo.

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We report a case of a 23-year-old Japanese woman who had severe hyperparathyroidism associated with chronic renal failure before the start of dialysis treatment. Her chief complaints were swelling and pain in both shoulders. Laboratory examination revealed renal failure (BUN 134 mg/dl, serum Cr 7.3 mg/dl), severe normocytic normochromic anemia (hemoglobin 4.3 g/dl), hypercalcemia (11.8 mg/dl), and hyperphosphatemia (9.7 mg/dl). Serum PTH levels were extremely increased (intact PTH >1,000 pg/ml: normal range 10-50 pg/ml). X-ray examination of the skull and shoulders showed a salt and pepper appearance, and cauliflower-like deformity of the distal end of both clavicles, respectively. Accelerated ectopic calcification was observed in the costal cartilages, internal carotid arteries, and splenic arteries. Ultrasonographic examination revealed enlargement of the four parathyroid glands. Thallium-technetium subtraction scintigraphy of the parathyroid glands showed increased uptake into the upper two. Renal needle biopsy revealed severe impairment of the interstitium and tubules with much milder changes in glomeruli. The etiology of the renal failure could not be identified. Hemodialysis, total parathyroidectomy and auto-transplantation into the forearm were immediately performed. The pathological diagnosis was chief cell hyperplasia of the parathyroid glands. Based on the presence of chronic renal failure, remarkable hyperphosphatemia with mild hypercalcemia, an unusually high level of serum PTH, and accelerated ectopic calcification, the patient was diagnosed to have severe secondary hyperparathyroidism caused by chronic renal failure with major impairment of the renal interstitium and tubules.

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OBJECTIVE: The tissue renin-angiotensin system and extracellular matrix are involved in the cardiovascular hypertrophy and remodeling induced by hypertension. In this study, we examined the gene expression of the tissue renin-angiotensin system and fibronectin in inbred Dahl Iwai salt-sensitive and salt-resistant rats. MATERIALS AND METHODS: Eight pairs of 6-week-old male Dahl Iwai salt-sensitive and salt-resistant rats were fed either a low- or high-salt diet (0.3% or 8% NaCl, respectively) for 4 weeks. Activities of the circulating renin-angiotensin system were measured by radioimmunoassay and the gene expression of tissue angiotensinogen, the angiotensin II type 1 receptor (AT1) and fibronectin were analyzed by Northern blot analysis. RESULTS: Salt loading significantly increased blood pressure and produced cardiovascular hypertrophy and nephrosclerosis in the salt-sensitive rats. Activities of the circulating renin-angiotensin system were lower in salt-sensitive rats than in salt-resistant rats fed the low-salt diet, and salt loading lowered these activities in salt-resistant rats but not in salt-sensitive rats. In salt-resistant rats, salt loading increased renal, cardiac and aortic angiotensinogen, AT1 and fibronectin messenger (m)RNA expression except for aortic fibronectin mRNA expression. In contrast, in the salt-sensitive rats, salt loading stimulated the expression of cardiac fibronectin and aortic angiotensinogen, AT1 and fibronectin mRNAs. Furthermore, the cardiac and aortic fibronectin mRNA levels in salt-sensitive rats were higher than those in salt-resistant rats when both strains were fed the high-salt diet. CONCLUSIONS: These results demonstrate that the expression of tissue angiotensinogen, AT1 and fibronectin mRNAs is regulated differently in Dahl Iwai salt-sensitive and salt-resistant rats, and indicate that salt-mediated hypertension activates the cardiac fibronectin gene independently of the tissue renin-angiotensin system and stimulates the aortic fibronectin gene with activation of the tissue renin-angiotensin system.

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BACKGROUND: Macrophage-type nitric oxide synthase (NOS-II) is expressed in glomerular mesangial cells in response to inflammatory cytokines. Nitric oxide (NO) has antithrombotic and cytostatic activities in glomerular diseases. Recent studies have suggested that several vasoactive substances and growth factors modulate NO production in a tissue-specific manner. The aim of this study was to examine whether angiotensin II and transforming growth factor-beta (TGF-beta) modulate cytokine-stimulated NO production and NOS-II gene expression in rat glomerular mesangial cells. METHODS: Cultured rat mesangial cells were incubated with interleukin-1 beta (IL-1 beta) for 24 hours. The effects of angiotensin II and TGF-beta on stimulated nitrite accumulation and NOS-II mRNA levels were determined. RESULTS: Angiotensin II and TGF-beta significantly decreased IL-1 beta-stimulated nitrite accumulation. The angiotensin type 1 receptor antagonist CV11974 prevented angiotensin II-mediated inhibition of NO production. TGF-beta-neutralizing antibody reversed the effect of TGF-beta without affecting angiotensin II-mediated inhibition of NO production. TGF-beta markedly decreased steady-state levels of NOS-II mRNA and the half-life of the message, whereas angiotensin II did not alter these parameters. CONCLUSIONS: These results suggest that in mesangial cells, angiotensin II and TGF-beta participate in the inhibitory regulation of cytokine-induced NO production. TGF-beta inhibits NO production by decreasing NOS-II mRNA levels, whereas angiotensin II may regulate NO production at the levels after NOS-II gene expression. An autocrine action of TGF-beta induced by angiotensin II is unlikely to contribute to angiotensin II-mediated inhibition of NO production.

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A 56-year-old man presented with transient anemia in minimal-change nephrotic syndrome. Following nephrotic syndrome, anemia suddenly appeared without renal dysfunction. The anemia might be attributable to hemodilution because of significant correlations between the values of hemoglobin concentration and serum total protein or blood urea nitrogen during the clinical course. A low serum level and a low urinary excretion of erythropoietin were found, and when nephrotic syndrome ameliorated with steroid therapy, urinary erythropoietin excretion and anemia disappeared. This case indicated disappearance of the exponential increase of endogenous erythropoietin in acute anemia in nephrotic syndrome probably due to urinary losses and altered biosynthesis of erythropoietin. We report a case of the simultaneous improvement of both nephrotic syndrome and anemia with steroid therapy.

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We studied the localization of angiotensinogen mRNA in rat nephron segments and the differences in angiotensinogen mRNA levels between male Sprague-Dawley rats at 6 and 12 wk of age using reverse transcription and polymerase chain reaction (RT-PCR). Each nephron segment of the rat kidney was microdissected. Total RNA was prepared and used in the following RT-PCR assay. The PCR products were size-fractionated by agarose gel electrophoresis, visualized with ethidium bromide staining, and identified by Southern blot analysis. The relative amounts of products were determined by densitometry. Strong bands corresponding to angiotensinogen mRNA were detected from proximal convoluted and straight tubules, and weaker bands were found in glomeruli. The signals in all tissues in 12-wk-old rats were weaker than those in 6-wk-old rats. Since local angiotensinogen is the unique substrate of the tissue renin-angiotensin system and exerts an autocrine-paracrine influence on renal function, the changes in tubular angiotensinogen may be related to physiological and morphological changes in the rat kidney during development.

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BACKGROUND: Renin is a rate-limiting enzyme for activity of the circulating renin-angiotensin system (RAS) and expression of the renin gene is regulated by a variety of stimuli. In this study, we examined a possible role of c-Jun in the transcription of renin gene. METHODS: The renin promoter, chloramphenicol acetyltransferase (CAT), fusion genes with or without c-Jun expression vector (pSV-c-Jun) were transfected into human embryonic kidney (HEK) cells, and the effects of c-Jun were examined by deletion and mutation analyses of CAT assay and by in vitro transcription-primer extension assay. We also examined the effects of c-Jun on DNA-binding activity to the renin promoter by electrophoretic mobility shift assay (EMSA). Furthermore, we examined the effects of c-Jun on transcription of the renin gene in enriched juxtaglomerular (JG) cells by cotransfection with pSV-c-Jun and by treatment with antisense c-jun oligodeoxynucleotides. RESULTS: Promoter activity of the renin gene was increased by c-Jun overexpression in HEK cells, and the proximal promoter region from -47 to +16 was sufficient for transcriptional activation by c-Jun. Although mutation of activator protein-1 (AP-1) element-like sequences in the proximal promoter did not affect c-Jun-mediated stimulation, mutation of the core promoter including the TATA box inhibited c-Jun-mediated transcription. The results of EMSA showed that c-Jun overexpression produced a binding of nuclear factor, which was HEK cell-specific and distinct from TATA box-binding protein and AP-1 family transcription factor, to the renin core promoter region (RC element) from -36 to -20. The overexpression of c-Jun activated the renin promoter in renin-expressing JG cells, and antisense c-jun decreased the activity of renin promoter and expression of renin mRNA in JG cells. CONCLUSIONS: These results indicate that the RC element plays a role in c-Jun-mediated transcriptional regulation of the renin gene in HEK cells, and suggest that c-Jun participates in the regulation of renin gene expression in JG cells of the kidney.

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1. We investigated the toxicity of cyclosporine A (CsA) with reference to the timing of its administration in rats. 2. To elucidate the time-dependent effects of CsA on renal function and survival rate, CsA (75 mg/kg per day) or vehicle was orally administered once daily at four different times (3, 9, 15 and 21 h after lights on; HALO) over a period of 21 days to male Wistar rats (n = 56) kept in rooms with a 12 h light-dark cycle. 3. On the 7th day after treatment, creatinine clearances (Ccr) of groups dosed at 3 and 9 HALO (inactive period) were not reduced in comparison with clearances of time-matched control rats, whereas Ccr significantly decreased in rats dosed at 15 and 21 HALO (active period). Cyclosporine A markedly increased urinary N-acetyl-beta-D-glucosaminidase (NAG) excretion in all dosed groups at the 7th day after treatment, except for rats dosed at 3 HALO. In rats dosed at 3 HALO, Ccr decreased progressively; however, it did not decrease progressively in rats dosed at 9 HALO. In surviving rats treated during the inactive period, urine NAG subsequently returned to control levels. Survival rates were greater in animals dosed during inactive periods than those in groups dosed during active periods. 4. Significant differences in CsA-induced toxicity were obvious as a result of the timing of its administration. A different time course between Ccr and urine NAG excretion was observed during repeated CsA administration. Degenerative changes in proximal tubules were demonstrated after chronic administration of CsA, suggesting that severe and persistent tubular damage cannot be assessed by urinary NAG excretion.

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Angiotensin type-1a (AT1a) receptor gene-knockout (AT1a-/-) mice exhibit chronic hypotension and renin overproduction. In the kidneys of AT1a-/- mice, the activity of neuronal type nitric oxide synthase (N-NOS) was histochemically detected by nicotinamide adenine dinucleotide phosphate (NADPH) diaphorase (NADPHd) reaction combined with N-NOS immunohistochemistry. The localization of renin was detected by immunohistochemistry and the results were analyzed morphometrically. The levels of N-NOS and renin mRNA in the renal cortical tissue were determined by reverse transcription-PCR and Northern blot analysis, respectively. In the renal sections from wild-type mice, NADPHd activity and N-NOS immunoreactivity were localized to the discrete region of the macula densa in contact with the parent glomerulus. In contrast, N-NOS-positive macula densa cells were distributed beyond the original location of the macula densa, occasionally extending to the opposite side of the distal tubules. The mean number of N-NOS positive macula densa cells was significantly increased in AT1a-/- mice (186 per 100 glomeruli) compared with wild-type mice (65 per 100 glomeruli). AT1a-/- mice showed 1.4-times higher N-NOS mRNA levels in the renal cortical tissues than wild-type mice. The plasma renin activity was significantly higher in AT1a-/- mice (205.5 +/- 26.1 ng/ml/hr) than in wild-type mice (8.0 +/- 0.2 ng/ml/hr). The renin-positive areas per glomerulus and renal renin gene expression were 12-times and 2.6-times higher in AT1a-/- mice than in wild-type mice, respectively. These abnormalities, however, were less remarkable in AT1a-/- mice compared with angiotensinogen-knockout mice. When AT1a-/- mice were fed a high-salt diet, the signal intensity of the NADPHd reaction and the number of positively-stained macula densa cells were significantly decreased. The levels of renal cortical N-NOS mRNA were also suppressed by the treatment. Dietary salt loading produced a parallel decrease in plasma renin activity, renal renin-immunoreactive areas, and the levels of renin mRNA without affecting systemic blood pressure. These results provide evidence for the possible involvement of N-NOS at the macula densa in the increased renin production in AT1a-/- mice.

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OBJECTIVE: Physiological roles of the renin-angiotensin system in maintaining blood pressure and sodium-water balance in angiotensinogen gene-knockout mice were evaluated with special reference to endogenous pressor substances. METHODS: Angiotensinogen-gene knockout mice and control mice were fed a 0.3 or 4% NaCl diet for 2 weeks. Systolic blood pressure and urinary excretions of electrolytes, creatinine, aldosterone, adrenaline, noradrenaline, dopamine and vasopressin were measured. RESULTS: About 60% of our angiotensinogen-gene knockout mice did not survive until weaning. These mice presented with hypotension and polyuria. Urinary excretion of aldosterone from such mice was significantly lower (not detected) than that from control mice (2.0+/-0.3 pg/mg creatinine). In contrast, urinary excretion of vasopressin from angiotensinogen-gene knockout mice (0.7+/-0.1 ng/mg creatinine) was greater than that from control mice (0.3+/-0.1 ng/mg creatinine), and those of adrenaline and of noradrenaline were similar for knockout and control mice. After salt loading (a 4% NaCl diet), angiotensinogen-gene knockout mice exhibited a significant increase in systolic blood pressure (from 68.3+/-2.9 to 95.9+/-5.9 mmHg), significant decreases in urinary excretions of adrenaline (from 65+/-8 to 40+/-7 pg/mg creatinine) and noradrenaline (from 467+/-48 to 281+/-41 pg/mg creatinine) and no change in excretion of vasopressin compared with such mice fed a 0.3% NaCl diet CONCLUSION: The present results with angiotensinogen-gene knockout mice confirm that the renin-angiotensin system plays fundamental roles in maintaining the blood pressure and sodium-water balance. Because the vasopressin and catecholaminergic systems may be altered by lack of angiotensin in angiotensinogen-gene knockout mice, these systems perhaps are not able to restore blood pressure and sodium-water depletion to normal levels in these mice.

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Angiotensinogen gene-knockout (Atg-/-) mice lacking angiotensin II exhibit chronic hypotension. The present study was designed to investigate pathophysiology of Atg-/- mice from the renal functional view. Wild-type (Atg+/+) and Atg-/- mice at 10 weeks of age were housed in metabolic cages for 24-hour urine collection. When provided free access to water, Atg-/- mice showed an increased urine output and a decreased urine osmolality compared with Atg+/+ mice. Urinary excretion and plasma levels of vasopressin were significantly higher in mutant mice than in wild-type mice. On the other hand, urinary excretion of aldosterone in mutant mice was suppressed to the levels under the detection limit of the assay system. The mean plasma aldosterone level of Atg-/- mice was suppressed to 30% of that of Atg+/+ mice. Plasma levels of creatinine, endogenous creatinine clearance, and urinary electrolyte excretion were not different between these mice. In Atg+/+ mice, urine osmolality was markedly increased from 1929 +/- 21 to 3314 +/- 402 mOsm/kg during water deprivation, whereas this parameter in Atg-/- mice did not change significantly (from 1413 +/- 121 to 1590 +/- 92 mOsm/kg). Urinary vasopressin excretion increased during water deprivation from 0.24 +/- 0.04 and 0.70 +/- 0.08 to 0.42 +/- 0.06 and 2.31 +/- 0.35 ng/mg creatinine in wild-type and mutant mice, respectively. Histologic study revealed interstitial inflammation, and atrophic changes in the tubules and papilla in Atg-/- mice. In conclusion, a genetic deficiency of angiotensinogen produced an impaired urine concentrating ability and tubulointerstitial lesions, indicating the critical role of angiotensinogen in developing normal tubular function and construction.

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The present study investigates whether neuronal type nitric oxide synthase (N-NOS) in the macula densa participates in the regulation of renal renin expression during altered dietary salt intake in angiotensinogen gene-knockout (Atg-/-) mice. Wild-type (Atg+/+) and Atg+/+ mice were fed a low-salt (0.04% NaCl), normal-salt (0.3% NaCl), or high-salt (4% NaCl) diet for 2 wk. Histochemical staining for NADPH diaphorase (NADPHd) and renin were analyzed morphometrically. Levels of N-NOS and renin mRNA in renal cortical tissues were determined by reverse transcription-PCR and Northern blot analysis, respectively. In animals fed a normal-salt diet, the renal expressions of N-NOS and renin were markedly increased in Atg-/- mice compared with Atg+/+ mice. When mutant mice were fed a high-salt diet, the signal intensity of the NADPHd reaction and the number of positively stained macula densa cells were significantly decreased. The levels of renal cortical N-NOS mRNA were also suppressed by the treatment. These changes were paralleled by decreases in renal renin-immunoreactive areas and the levels of renin mRNA. On the other hand, salt restriction did not produce further significant increases in the renal N-NOS and renin expressions in mutant mice, whereas a parallel inverse relationship was observed between these enzyme expressions and the levels of salt intake in wild-type mice. These results suggest that the N-NOS expression in the macula densa is inversely regulated by salt intake and that the enzyme activity is functionally linked to renal renin production. Salt-modulated renal N-NOS and renin expressions are independent on angiotensin formation in Atg-/- mice.

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Two subtypes of angiotensin II (Ang II) receptors, type 1 (AT1-R) and type 2 (AT2-R), have been identified in the heart. However, little is known about the regulation of cardiac AT1-R and AT2-R by Ang II in vivo. Thus, we examined cardiac AT1-R and AT2-R in angiotensinogen-deficient (Atg-/-) mice that are hypotensive and lack circulating Ang II. Cardiac Ang II receptors (Ang II-R) were assessed by radioligand binding with 125I-[Sar1,Ile8]-Ang II in plasma membrane fractions. AT1-R and AT2-R were distinguished using their specific antagonists CV-11974 and PD123319, respectively. Total densities of Ang II-R and AT1-R density were significantly greater in the Atg-/- mice than Atg+/+ mice (31.1+/-2.8 versus 18.8+/-2.1, 28.7+/-3.0 versus 16.9+/-2.3 fmol/mg protein, P<.01, respectively), and AT2-R showed a slight but not significant increase in Atg-/- mice relative to Atg+/+ control animals. Kd values were not different between the two groups. In contrast to binding experiments, levels of Ang II type 1a receptor (AT1a-R) and AT2-R mRNA did not differ between Atg-/- and Atg+/+ mice. These results suggest that lack of Ang II may upregulate AT1-R through translational and/or posttranslational mechanisms in Atg-/- mice.

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The angiotensinogen (AGT) gene M235T variant is associated with essential hypertension and elevated plasma AGT concentrations, although the underlying mechanisms are unknown. Recent studies have suggested that AGCE 1 (human AGT gene core promoter element 1) located in the 5' upstream core promoter region (position -25 to -1) of the human AGT gene has an important part in the expression of AGT mRNA by binding with transcription factor AGCF 1 (human AGT gene core promoter element binding factor 1), and a mutation at -20 from adenine to cytosine (A-20C) increases the level of expression of this transcript. We therefore examined subjects with this mutation to study the association with increased plasma AGT concentrations and with essential hypertension. One hundred eighty-eight subjects receiving no antihypertensive medication were examined with regard to the correlation between A-20C and plasma AGT concentrations, and 234 subjects were studied with respect to the association between A-20C and essential hypertension. A-20C was determined by polymerase chain reaction-restriction fragment length polymorphism analysis with EcoOR 109I. Multiple regression analysis showed a weak but significant correlation between A-20C and plasma AGT concentrations (P=.047) and essential hypertension (P=.049). The results suggest that A-20C may underlie the increase in plasma AGT concentrations and be involved in the development of essential hypertension.

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There is now convincing evidence that various tissues express their own tissue renin-angiotensin system, which may be regulated independently of the systemic renin-angiotensin system. However, little information is available on the regulation of the tissue renin-angiotensin system. We investigated the regulation of tissue angiotensinogen gene expression with respect to the development of hypertension. We measured basal and lipopolysaccharide-stimulated plasma angiotensinogen concentrations by radioimmunoassay and examined the expression of tissue angiotensinogen by Northern blot analysis in spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY) at 4 and 13 weeks of age. Basal plasma angiotensinogen concentration in SHR was comparable to that in WKY at 4 weeks of age and was significantly higher than that in WKY at 13 weeks of age. Lipopolysaccharide induced a significant increase in plasma angiotensinogen concentration in both WKY and SHR at 4 and 13 weeks of age. At 4 weeks of age, the basal levels of angiotensinogen mRNA in the liver, fat, adrenal, and aorta were higher in WKY than in SHR. At 13 weeks of age, the basal levels of angiotensinogen mRNA in the fat, adrenal, aorta, spleen, and kidney were higher in WKY than in SHR, while that in the liver did not differ significantly between the two strains. At 4 weeks of age, pretreatment with lipopolysaccharide increased the angiotensinogen mRNA levels in the liver, fat, adrenal, and aorta in both WKY and SHR. At 13 weeks of age, pretreatment with lipopolysaccharide increased the angiotensinogen mRNA levels in the liver, aorta, and adrenal; decreased those in the spleen; and had no effect in the kidney in both WKY and SHR. Interestingly, lipopolysaccharide increased the angiotensinogen mRNA level in fat only in SHR, with no effect in WKY, at 13 weeks of age. Lipopolysaccharide stimulated tumor necrosis factor-a mRNA expression in fat of WKY and SHR, and the increase in tumor necrosis factor-alpha mRNA level in SHR was significantly greater than that in WKY. Therefore, the increased tumor necrosis factor-alpha mRNA expression may be involved in the increased lipopolysaccharide-induced expression of angiotensinogen gene in fat of SHR at 13 weeks of age. These data suggest that the transcriptional and probably posttranscriptional regulation of angiotensinogen mRNA differs between SHR and WKY, that the regulation of angiotensinogen gene expression is tissue-specific, and that the altered expression of the angiotensinogen gene may be involved in the development of hypertension.

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The protein product of the retinoblastoma susceptibility gene, RB, is a nuclear phosphoprotein that modulates transcription of genes involved in growth control via interactions with transcription factors. Renin is a rate-limiting enzyme of the renin-angiotensin system that regulates blood pressure and water-electrolyte balance. Renin gene expression is regulated in a tissue-specific and developmentally linked manner. Similarly, the expression of RB is controlled in a differentiation-linked manner. Thus, to investigate whether RB is involved in the regulation of renin gene expression, we examined the effects of RB on transcriptional activity of the mouse renin (Ren-1C) promoter. The Ren-1C promoter contains two transcriptionally important elements; the RU-1 (-224 to -138) and RP-2 (-75 to -47) elements. RB activated the Ren-1C promoter in human embryonic kidney cells. The promoter element responsible for RB-mediated transcriptional regulation was the RP-2 element. The results of DNA-protein binding experiments showed that RB increased nuclear binding activity to the RP-2 element, and site-directed mutation which disrupted binding of nuclear factors to the RP-2 element markedly reduced RB-mediated activation of Ren-1C promoter in human embryonic kidney cells. These results indicate that the RP-2 element plays an important role in RB-mediated transcriptional regulation of Ren-1C promoter activity in human embryonic kidney cells, thereby suggesting an interesting mechanism by which RB may modulate the renin-angiotensin system.

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A close relationship between obesity and hypertension has been recognized, and plasma angiotensinogen concentrations (p-AGT) have been reported to correlate with blood pressure (BP). However, little is known about AGT in obese patients with hypertension. To define the role of AGT in obese hypertension, we measured p-AGT in obese patients. The subjects were 42 obese patients diagnosed on the basis of a body mass index (BMI) of more than 25 kg/m2, and 21 sex- and age-matched nonobese patients, whose BMI was less than 25 kg/m2. The hypertensive patients had not previously received antihypertensive drugs. P-AGT (P < .05) and mean BP (P < .0001) was increased in the obese patients as compared with the nonobese patients. Positive correlations were observed between BMI and p-AGT, mean BP and p-AGT, and BMI and mean BP (all P < .05). However, after adjustment for blood pressure, p-AGT was not different between groups, and after adjustment a positive correlation remained only between BMI and mean BP. These results suggested the possible involvement of increased p-AGT in hypertension in obese patients, although this may be a secondary change to hypertension or obesity.

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