Biomedical subjects

M Yasujima

Publications and source records attributed to M Yasujima.

At least 37 records · Page 2Linked to original sources

PubMed1999

[Renal sodium transport abnormality: Gitelman's syndrome and renal sodium transporter].

Recent studies using molecular biological methods have enabled us to identify the genetic abnormality in renal electrolyte metabolism. In renal tubules, diuretic sensitive Na transporter systems are present, and key molecules have been cloned. Thiazide-sensitive Na-Cl contransporter (TSC) is one of the molecules localized in the distal convoluted tubule, whose genetic abnormality causes Gitelman's syndrome (a variant of Bartter's syndrome characterized by dehydration, hypokalemic metabolic alkalosis, secondary aldosteronism lacking hypertension, hypomagnesemia, and hypocalciuria). We identified a mutation in TSC (Leu to Pro change at 623 amino acid position, L623P) in familial Gitelman's syndrome, and we confirmed the loss of TSC function by this mutation in a functional expression system using mammalian cells. This L623P mutation has been found in other patients with Gitelman's syndrome living in the northern part of Japan.

Bartter Syndrome↗

PubMed1998

Different roles of brain interleukin 1 in the adrenocorticotropin response to central versus peripheral administration of lipopolysaccharide in the rat.

Although it is well established that peripheral administration of endotoxin activates the hypothalamic-pituitary-adrenal (HPA) axis, information is very limited regarding whether central administration of endotoxin can similarly stimulate the endocrine axis. Moreover, it is also unknown whether a difference exists in the mode of involvement of brain-derived cytokines in determining the HPA response to peripheral vs central administration of endotoxin. In the present study, the authors attempted to gain more knowledge on these issues focusing on interleukin (IL) 1 in the brain, one of key pro-inflammatory cytokines mediating the immuno-endocrine network. In male rats, both intravenous (i.v., 100 micrograms/kg body weight) and intracerebroventricular [i.c.v. (the 3rd ventricle), 10 micrograms] injections of Escherichia coli lipopolysaccharide (LPS) caused a significant elevation of adrenocorticotropin (ACTH) levels in plasma, even though peaked ACTH responses occurred earlier after the i.v. (60 min post-injection) than the i.c.v. (120 min post-injection) LPS. Although the ACTH response to i.c.v. LPS was significantly suppressed by a prior (5 min) i.c.v. administration of IL-1 receptor antagonist (IL-1Ra, 1 microgram), the hormonal response to i.v. LPS was not. That this dose of IL-1Ra was not biologically a small dose was indicated by another experiment that the same dose of i.c.v. IL-1Ra was able to significantly suppress the ACTH response to an i.c.v. injection of recombinant human IL-1 beta (50 ng). These results suggest that i.c.v. LPS, as i.v. LPS, can stimulate ACTH secretion in the rat, and this hormonal response may, at least in part, be mediated by brain-derived IL-1. Although there is one previous study reporting an important role of central IL-1 in mediating the HPA response to systemic LPS treatment, our present data suggest that such a mechanism may not operate before and during an early, peak phase of ACTH secretion after i.v. LPS.

Adrenocorticotropic Hormone↗

PubMed1998

Effect of chronic neutral endopeptidase inhibition on cardiac hypertrophy after experimental myocardial infarction.

Candoxatril is an inhibitor of neutral endopeptidase, a membrane-bound enzyme that degrades atrial natriuretic peptide. The effects of candoxatril on hemodynamic parameters and cardiovascular hypertrophy were evaluated in the rat model of myocardial infarction. Myocardial infarction was induced by left coronary artery ligation in rats and they were treated either with candoxatril (10mg/kg per day) or a vehicle for up to 4 weeks. Systolic blood pressure and body weight did not change for up to 4 weeks between the 2 groups. At the end of treatment, hemodynamic parameters were measured, and then plasma, heart, lungs and kidneys were collected. Kidney neutral endopeptidase, as measured by the quantitative autoradiographic method, was significantly inhibited in candoxatril-treated rats compared with that in controls (66.6+/-3.2% of control, p<0.001). On the contrary, there were no significant differences in right atrial pressure, left ventricular end-diastolic pressure, systemic pressure, and plasma level of atrial natriuretic peptide between the 2 groups. There were also no significant differences in cardiac weight and lung weight. These data indicate that inhibition of neutral endopeptidase by candoxatril at a dose of 10 mg/kg per day did not oppose cardiac hypertrophy in the rat model of myocardial infarction in spite of significant neutral endopeptidase inhibition.

Animals↗

PubMed1998

[Endothelial nitric oxide synthase gene polymorphism and hypertension].

Nitric oxide (NO) is produced by endothelial cells and serves as a potent vasodilator. Several lines of evidence have shown that NO plays an important role in the regulation of blood pressure and regional blood flow. Endothelial NO synthase (eNOS) gene polymorphisms exhibit a positive association in myocardial infarction and smoking-dependent risk of coronary artery disease. However, the relationship between eNOS gene polymorphisms and hypertension is controversial. To examine the possible involvement of the eNOS gene in the genetic basis for hypertension, we identified genotypes for 2 eNOS gene polymorphisms in 166 hypertensive and 174 normotensive populations in Aomori prefecture, in northern Japan. The specific genotypes for Glu298Asp missense variant and variable numbers of tandem repeats in intron 4 (eNOS 4b/4a) were isolated using allele specific gene amplification and restriction fragment length polymorphism. The 298Asp variant was significantly correlated to hypertension in these groups (odds ratio, 1.8; 95% confidence interval, 1.1-3.2). The allelic frequencies of 298Asp for Glu298 in hypertensive patients were significantly higher than those in normotensive subjects (0.136 vs 0.083, p < 0.05). However, disequilibrium of eNOS4b/4a was absent between these 2 groups. These results suggest that Glu298Asp is a genetic susceptibility factor for hypertension.

Aged↗

PubMed1997

Angiotensin converting enzyme gene polymorphism and its enzyme activity in serum in young Japanese females.

To assess the potential association between the angiotensin converting enzyme (ACE) gene polymorphism and the activity of the renin-angiotensin system in a Japanese population, we determined the ACE genotype and its enzyme activity in serum in 108 young Japanese females. Genomic DNA was extracted from blood samples and amplified by polymerase chain reaction (PCR). PCR primers flanked the polymorphic region in intron 16 of the ACE gene. The distribution of the DD, ID and II ACE genotypes was 10, 55 and 35%, respectively. The estimated allele frequencies of the deletion and the insertion were 0.375 and 0.625, respectively. The mean serum ACE activity in DD subjects was about 1.4 times that of II subjects (p < 0.01), with ID subjects having intermediate levels (p < 0.05), whereas the renin profile were not statistically different among the three groups. These results indicate a significant association between ACE gene polymorphism and serum ACE activity levels, suggesting a mechanism by which genotype might have a hearing on the physiology of the renin-angiotensin system axis.

Adolescent↗

PubMed1996

Cardiomegaly and vasoactive hormones in rats with chronic myocardial infarction: long-term effects of chlorothiazide.

1. The effects of prolonged chlorothiazide treatment of left ventricular failure on cardiac hypertrophy, circulating vasoactive hormones and exchangeable body sodium were examined in rats with chronic myocardial infarction induced by left coronary artery ligation. Chlorothiazide therapy commenced either immediately or 2 weeks after infarction. For 4 weeks, the rats were given either chlorothiazide (50 mg day-1 kg-1) in their drinking water or drinking water alone. 2. Cardiac weight increased in untreated rats with infarction in comparison with sham-operated controls, indicating the presence of chronic left ventricular dysfunction, although exchangeable body sodium, plasma renin activity, plasma vasopressin and plasma osmolality remained unchanged. 3. Chlorothiazide raised haematocrit and plasma renin activity equally in rats with and without infarction, although exchangeable body sodium, plasma vasopressin and plasma osmolality were not changed by the treatment. Plasma atrial natriuretic peptide was 2-fold higher in rats with infarction and this response was not affected by chlorothiazide treatment. Chlorothiazide therapy did not prevent or reverse cardiac hypertrophy. 4. Chronic diuretic therapy in this experimental model of heart failure did not reduce extracellular sodium, plasma vasopressin or the extent of ventricular hypertrophy, possibly because the condition was associated with activation of the renin-angiotensin system.

Animals↗

PubMed1996

Effects of benidipine, a calcium antagonist, on urinary kallikrein excretion and renal impairment in experimental diabetes.

OBJECTIVE: To assess the long-term effects of different antihypertensive agents on urinary protein excretion and kallikrein excretion in diabetic rats with renal impairment. METHODS: Uninephrectomized streptozotocin diabetic Wistar-Kyoto rats were randomly assigned to receive vehicle, a calcium antagonist (benidipine) or an angiotensin converting enzyme inhibitor (captopril) for up to 12 weeks. Active kallikrein was determined by its kininogenase activity, and generated kinins were measured by radioimmunoassay. Total kallikrein was also determined by measuring kininogenase activity after inactive kallikrein had been activated with trypsin. RESULTS: Urinary protein excretion increased significantly in diabetic rats compared with non-diabetic rats. Urinary active kallikrein excretion was significantly reduced in diabetic rats, whereas urinary total kallikrein excretion was unchanged, resulting in a reduced percentage of active to total kallikrein compared with that in non-diabetic rats. Benidipine and captopril reduced blood pressure and attenuated the development of diabetic renal impairment in a similar manner. However, only benidipine attenuated the decreases in urinary active kallikrein excretion and the ratio of active to total kallikrein in diabetic rats. CONCLUSIONS: Although pathophysiological relevance of impaired urinary kallikrein activation to the development of diabetic renal impairment remains to be determined, our result might suggest a new mechanism by which calcium antagonists protect the kidney from diabetic renal impairment.

Analysis of Variance↗

PubMed1996

[Peripheral lymphocyte subset of patients with pancreatic diabetes mellitus--about a decreased ratio of T-LGL and ability of host defense].

Patients with diabetes mellitus (DM) often suffer from various and severe infection. Patients with pancreatic DM have malnutrition due to chronic pancreatitis. Therefore it is believed that patients with pancreatic DM have a lower ability of host defence to infectious diseases than normal subjects. We examined the primpheral lymphocyte subsets (T cell, B cell, NK cell, CD3+ 56+ T) of eighteen patients (males, age = 52.8 +/- 12.7 years old, mean +/- SD) with pancreatic DM by two color flow-cytometry to evaluate the lymphocyte function. Ratios of T cell (T%, 66.9 +/- 9.3%, mean +/- SD). B cell (B%, 13.1 +/- 5.8%) and NK cell (Nk%, 19.3 +/- 8.7%) to total peripheral lymphocytes of patients with pancreatic DM were not significantly different from those (T% = 66.4 +/- 7.8%, B% = 13.5 +/- 6.7%, NK% = 19.9 +/- 9.1%) of thirteen normal subjects (males, age = 51.2 +/- 13.1). CD3+56+ T cell % (4.1 +/- 1.9%) of patients with pancreatic DM was lower than that (6.0 +/- 3.0%) of normal subjects (p < 0.05). CD3+56+ T cells have cytotoxic activity and it is likely that this activity is similar to that of NK cells. These results suggested that a decrease in peripheral CD3+56+ T cell % is a factor showing a weak host defense mechanism to infectious diseases in patients with pancreatic DM.

Adult↗

PubMed1996

Cardiac angiotensin converting enzyme and endothelin receptor in rats with chronic myocardial infarction.

To ascertain the pathophysiological roles of the renin-angiotensin system and endothelin in heart failure and cardiac hypertrophy, we assessed changes in cardiac angiotensin converting enzyme (ACE) and endothelin-1 (ET-1) receptor using rats in which myocardial infarction was induced by left coronary ligation. The animals were decapitated 1 or 8 months after the operation. Cardiac ACE and ET-1 receptor were quantified by computerized in vitro autoradiography using 125I-MK351A (a lisinopril derivative) and 125I-ET-1. One month after myocardial infarction, cardiac weight and plasma atrial natriuretic peptide had increased in rats with infarction, compared to sham-operated controls, indicating the presence of chronic left ventricular dysfunction, although exchangeable body sodium and plasma renin activity were unchanged. Cardiac ACE increased markedly in the infarcted area and moderately in hypertrophied myocardium without any change in affinity compared to sham-operated rats. On the other hand, there was no change in cardiac ET-1 receptors in infarcted rats. The same results were found even at 8 months after myocardial infarction. The present study indicates that cardiac ACE may participate in tissue repair at the site of myocardial infarction and may also play a role in the pathophysiology of cardiac hypertrophy in rats with chronic heart failure. However, the present results do not reveal whether ET-1 receptor participates in the pathophysiology of cardiac hypertrophy in this model.

Angiotensin II↗

PubMed1996

[Current topics on the detection, evaluation and treatment of hypertension].

Since hypertension is one of the major important risk factors for coronary heart disease and the most important risk factor for cerebrovascular diseases, recent progress in the detection and management of hypertension has contributed to the morbidity and mortality declines. However, some problems of how to detect, evaluate and treat hypertension in clinical practice have remained to be solved. First, classifications of blood pressure monitoring at home and/or work and 24-hour ambulatory blood pressure monitoring based on impact on risk of cardiovascular diseases are not available, whereas there is increasing evidence that out-of-office measurements of blood pressure are more helpful in detecting hypertension, evaluating severity of hypertension and judging the effectiveness of treatment, than in-office measurements. Secondly, nonpharmacological treatment of hypertension which include weight reduction, increased physical activity, and moderation of dietary sodium and alcohol intake offer multiple benefits at little cost and with minimal risk. However, the role of nonpharmacological treatment to reduce morbidity and mortality of cardiovascular diseases has not been clearly established. In addition the evidence from randomized trials, directly comparing drug therapy and nondrug therapy of mild hypertension is not in favor of the cost-effectiveness nor even of the medical effectiveness of the nonpharmacological treatment of mild hypertension. Finally, the benefits of therapeutic strategies for treating patients with mild hypertension, elderly patients with isolated systolic hypertension and patients with cardiovascular disease complication have not been evaluated in long-term intervention trials especially in Japan.

Antihypertensive Agents↗

PubMed1995

Effects of recombinant human erythropoietin on blood pressure and renal function in SHR with chronic renal failure.

1. The effects of chronic administration of erythropoietin (EPO) on blood pressure and renal function in rats with ablation of renal mass were assessed. 2. Spontaneously hypertensive rat were subjected to 5/6 nephrectomy (5/6Nx). Four weeks after the operation, the rats were randomly allocated to vehicle, EPO 20IU/kg i.p., or EPO 100 IU/kg i.p. (both given twice a week) for 4 weeks. 3. Marked anaemia was noted in SHR-5/6Nx. EPO caused a significant increase in haematocrit at a high dose but not at a low dose. A dose dependent relationship was noted in the EPO-induced rise in the systolic blood pressure. 4. EPO dose-dependently increased urinary protein excretion. It also increased blood urea nitrogen and serum creatinine levels. 5. These results suggest that EPO ameliorates anaemia and severely accelerates renal failure in SHR-5/6Nx. They also suggest that anaemia can be a haemodynamically favorable adaptation to chronic renal disease and that its correction may have adverse renal haemodynamic and structural consequences.

Anemia↗

PubMed1995

Do kinins mediate cardioprotective and renoprotective effects of cilazapril in spontaneously hypertensive rats with renal ablation?

1. We assessed the potential of the kallikrein-kinin system in mediating the cardioprotective and renoprotective effects of an angiotensin-converting enzyme inhibitor (ACEI), cilazapril (CIL) in rats with renal ablation. 2. Eight week old spontaneously hypertensive rats (SHR) were subjected to 5/6 nephrectomy. One week after the operation, the rats were divided into 5 groups: (i) vehicle; (ii) CIL 1 mg/kg per day per os (p.o.); (iii) Hoe140 (HOE) 70 mu g/kg per day given intraperitoneally (i.p.); (iv) CIL 1 mg/kg per day p.o. plus HOE 7 mu g/kg per day i.p.; (v) CIL 1 mg/kg per day p.o. plus HOE 70 mu g/kg per day i.p. The treatment lasted for 4 weeks. 3. CIL alone significantly reduced systolic blood pressure, urinary protein excretion, heart weight and serum creatinine level. HOE alone did not induce any significant changes in these parameters. CIL in combination with HOE (7 or 70 mu g/kg per day) did not induce any changes in these parameters, in addition to those associated with the effects of CIL alone. 4. These results indicate that the kallikrein-kinin system might not play a major role in the cardioprotective and renoprotective effects of ACE inhibitors in the rat remnant kidney model of chronic renal failure.

Adrenergic beta-Antagonists↗

PubMed1995

Cardiovascular and renal protective effects of losartan in spontaneously hypertensive rats with diabetes mellitus.

1. Cardiovascular and renal benefits of a specific angiotensin II (AII) receptor antagonist, losartan (LOS), were assessed in diabetic rats with renal impairment. 2. Uninephrectomized SHR made diabetic by streptozotocin administration were given LOS (5 mg/kg per day, i.p.) alone, captopril (CAP) (50 mg/kg per day, i.p.) alone, or a combination of CAP and LOS via osmotic minipumps for 8 weeks. 3. Both CAP alone and LOS alone completely blocked the development of hypertension in diabetic SHR in the same manner. CAP + LOS did not enhance the antihypertensive effects of LOS alone or CAP alone. 4. CAP + LOS, LOS alone and CAP alone significantly decreased urinary protein excretion and serum creatinine to the same extent. 5. These results indicate that both LOS and CAP exert antihypertensive and renoprotective effects in this model: these actions are mainly through inhibition of AII production.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed1995

Antihypertensive and renal-protective effects of losartan in streptozotocin diabetic rats.

OBJECTIVE: To assess the renal benefits of a specific angiotensin II receptor antagonist, losartan, in diabetic rats with renal impairment. DESIGN AND METHODS: Uninephrectomized streptozotocin diabetic spontaneously hypertensive rats (SHR) were randomly assigned to receive vehicle, or to receive losartan or captopril, or both, intraperitoneally via osmotic minipumps for 8 weeks. RESULTS: Blood pressure and urinary protein excretion in the diabetic SHR increased progressively during the experimental period. Both captopril treatment and losartan treatment completely blocked the development of hypertension in diabetic SHR. Simultaneous administration of captopril and losartan did not enhance the antihypertensive effects of losartan treatment or captopril treatment. Furthermore, losartan treatment, captopril treatment and losartan + captopril treatment all significantly decreased urinary protein excretion, urinary albumin excretion and serum creatinine to the same extent. These effects were sustained for the entire experimental period and were not associated with any significant changes in body weight, urine volume, urine sugar and urinary electrolytes excretion. These results were confirmed by morphological analysis of kidneys in each group of rats. Losartan treatment, captopril treatment and losartan+captopril treatment all significantly and effectively protected against an increase in the percentage of focal glomerular sclerosis. Losartan treatment and captopril treatment both significantly attenuated the increase in heart weight: body weight ratio. The heart weight: body weight ratio in the losartan-treated group was significantly lower than in the captopril-treated group. CONCLUSIONS: These results indicate that hypertension could accelerate diabetic renal impairment and that losartan has antihypertensive and renoprotective effects in this rat model. They also suggest that the antihypertensive and renoprotective effects of captopril treatment in this rat model are caused mainly by inhibition of angiotensin II production rather than stimulation of the kallikrein-kinin system or of vasodilator prostaglandins. The difference in potency between losartan treatment and captopril treatment to attenuate the increase in heart weight: body weight ratio might partly explain the existence in the heart of angiotensin-forming pathways, which are not dependent on angiotensin converting enzyme.

Angiotensin II↗

PubMed1995

Endothelin receptors in ischemic rat brain and Alzheimer brain.

Endothelin (ET) binding sites in male Wistar rat brains subjected to a 20-min four-vessel occlusion (transient forebrain ischemia model) which induces hippocampal neuron death, and in human brains with Alzheimer disease, were mapped by quantitative in vitro autoradiography employing [125I]ET-1 as a radioligand. Rats were decapitated 4 or 7 days after ischemia. In the rat brain, the [125I]ET-1 binding sites were remarkably increased in the hippocampal CA1 and dentate gyrus, ventral thalamic nucleus, and cortical vessels 4 and 7 days after ischemia, when many reactive astroglia were observed. The [125I]ET-1 binding sites decreased in the cerebral cortex affected by Alzheimer disease. The binding was abolished by 1 microM unlabeled ET-1, ET-3, sarafotoxin S6b, and BQ788 (an ETB antagonist) but not by BQ123 (an ETA antagonist), suggesting that the [125I]ET-1 binding sites are as ETB receptors. The present findings raise the possibility that a glial ET system could be responsible for the occurrence of ischemic neuron cell death.

Alzheimer Disease↗

PubMed1995

Kinin and angiotensin II receptor antagonists in rats with chronic renal failure: chronic effects on cardio- and renoprotection of angiotensin converting enzyme inhibitors.

OBJECTIVE: To assess the potential of the kallikrein-kinin and renin-angiotensin systems in mediating the cardio- and renoprotective effects of angiotensin converting enzyme (ACE) inhibitors in rats with chronic renal failure. MATERIALS AND METHODS: Spontaneously hypertensive rats (SHR) and normotensive control Wistar-Kyoto (WKY) rats subjected to five-sixths nephrectomy were randomly assigned to treatment with vehicle, a kinin antagonist (Hoe 140) or an ACE inhibitor (cilazapril) or both drugs, intraperitoneally via osmotic minipumps for 4 weeks. In addition, the effects of a chronic infusion of a specific angiotensin receptor antagonist (losartan) alone or in combination with an ACE inhibitor (enalapril) were also investigated in nephrectomized SHR for 2 weeks. RESULTS: In nephrectomized SHR and WKY rats, cilazapril alone significantly reduced systolic blood pressure, urinary protein excretion, heart weight and serum creatinine. In nephrectomized SHR, Hoe 140 alone or cilazapril in combination with Hoe 140 (7 or 70 mu g/kg per day) induced no changes in these parameters, other than those associated with the effects of cilazapril alone. In nephrectomized WKY rats, cilazapril in combination with Hoe 140 (70 mu g/kg per day) slightly, but not significantly, attenuated the antihypertensive effect of cilazapril but did not affect the other parameters. These results were confirmed by morphological analysis of kidneys. All the drug regimens provided effective protection against an increase in focal glomerular sclerosis. Enalapril did not modify the antihypertensive and renoprotective effects of losartan in nephrectomized SHR. CONCLUSIONS: The present results indicate that the kallikrein-kinin system might not be a major factor in the cardio- and renoprotective effects of ACE inhibitors in rats with chronic renal failure.

Adrenergic beta-Antagonists↗

PubMed1994

Changes of plasma lipid and lipoproteins by rehabilitation therapy for stroke.

Changes of the plasma levels of lipid by rehabilitation therapy for approximately 10 weeks were studied in 14 cases of stroke. Hypercholesterolemia or hypertriglyceridemia was present in a half cases of stroke, and HDL cholesterol was lower than the normal level in most cases before starting rehabilitation therapy. After rehabilitation therapy, hypertriglyceridemia was normalized in most cases. On the other hand, the plasma levels of cholesterol and LDL cholesterol were decreased slightly. HDL cholesterol was increased and atherogenic index was improved by rehabilitation therapy.

Cerebrovascular Disorders↗

PubMed1994

[Activity and localization of neutral metalloendopeptidase (EC 3.4.24.11) (NEP), the degradative enzyme for atrial natriuretic peptide (ANP), in rat kidney].

Atrial natriuretic peptide (ANP) is degraded by neutral metalloendopeptidase (EC 3.4.24.11) (NEP), and the kidney is the major site of ANP clearance. The regional distribution of NEP in rat kidney was investigated by an enzymatic method and by in vitro autoradiography. The activity of NEP, measured with an enzymatic fluorimetric method employing N-dansy 1-D-alanyl-glycy 1-L-4-nitrophenylalany 1-glycine as a synthetic substrate, was 18 times higher in the outer stripe and 8 times higher in the inner cortex than in the outer cortex. Low concentrations of NEP were found in the outer cortex, in the inner stripe and in the inner medulla. NEP activity in rat kidney was inhibited by specific NEP inhibitors (phosphoramidon, thiorphan, SCH39370, SCH47896 and SCH48446) at micromolar concentrations. SCH47896 is a phenolic derivative of SCH39370 which can be radioiodinated with 125I. SCH48446 is a di-iodo analog of SCH47896. Thus, [125I]SCH47896 retains the full enzymatic inhibitory activity and full biological potency to bind to the active site of NEP. Autoradiographs using [125I]SCH47896 demonstrated maximal bind to regions of the outer stripe of the outer medulla and to the inner cortex, which was consistent with binding to the deep proximal tubules. These bindings were displaced in a dose-dependent manner by NEP inhibitors. Enalaprilat did not displace [125I]SCH47896 binding. EDTA inhibited these bindings by 90%. The present result suggests that degradation of ANP by NEP occurs mainly in the deep proximal tubules, and that the proximal convoluted tubule in the outer cortex is not a major site of location of NEP.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗