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Biomedical subjects

H Nonoguchi

Publications and source records attributed to H Nonoguchi.

At least 19 recordsLinked to original sources
PubMed2001

Physiological effects of vasopressin and atrial natriuretic peptide in the collecting duct.

Vasopressin plays a primary role in the concentration of urine to maintain body fluid homeostasis. The collecting duct as well as thick ascending limb is a major target site of vasopressin. The antidiuretic action of vasopressin is mediated by the V2 receptor in the basolateral membrane of principal cells in the collecting ducts. The binding of vasopressin to V2 receptors causes an activation of adenylate cyclase and a synthesis of cAMP. Vasopressin regulates water and ion transport through V2 receptor-mediated ion channels and transporters. In contrast, the V1a receptor mainly in the luminal membrane of distal nephron regulates basolateral V2 receptor-mediated action with regard to water and ion transport through the activation of G(q/11) and phosphoinositide turnover. Guanylate cyclase forms three types of ANP receptors, although NPR-A and B (GC-A and B) are biologically active and related to the synthesis of cGMP. Urodilatin, synthesized by the kidney, causes natriuresis by binding to GC-A in the collecting ducts. ANP causes diuresis and natriuresis, at least in part by inhibiting the V2 receptor-mediated action of AVP in the collecting ducts. The site of interaction of ANP and AVP is post cAMP synthesis, at least in the collecting ducts. The roles of AVP and ANP under pathophysiological conditions have been reported.

Animals↗
PubMed2001

Intranephron localization and regulation of the V1a vasopressin receptor during chronic metabolic acidosis and dehydration in rats.

The intrarenal localization and role of the V1a vasopressin receptor in body fluid homeostasis are unclear. We investigated the intranephron localization of V1a receptor mRNA and protein using reverse transcription (RT)-competitive polymerase chain reaction (PCR) and immunohistochemistry with a specific polyclonal antibody. To determine whether the V1a receptor is involved in the regulation of acid-base balance, we also examined the effects of acute and chronic metabolic acidosis and dehydration on V1a receptor expression. V1a mRNA was expressed most abundantly in the cortical collecting ducts (CCD) and decreased in the deeper CD. Expression in the glomeruli and thick ascending limbs was low. The immunohistochemical study revealed the presence of the V1a receptor in the glomeruli, the thick ascending limbs and the CD. Dehydration decreased V1a mRNA expression in the CD. Chronic metabolic acidosis increased V1a receptor mRNA expression in the CD but decreased V2 receptor mRNA expression. Western blot analysis revealed up-regulation of the V1a receptor protein in chronic metabolic acidosis. Incubation of microdissected CCD or outer medullary CD (OMCD) in a low-pH (or or low-HCO3-) medium increased the levels of V1a receptor mRNA but decreased V2 receptor mRNA expression. Incubating OMCD with arginine vasopressin (AVP) and the V1a receptor antagonist (OPC21268) increased V2 receptor mRNA expression compared with incubation with AVP alone. These data suggest that V1a receptors are present primarily in the principal and intercalated cells in the CD and that these receptors are involved in the regulation of water and acid-base balance.

Acidosis↗
PubMed2000

Patients with renal hypouricemia with exercise-induced acute renal failure and chronic renal dysfunction.

We here report the case of a 38-year-old male with back pain and vomiting occurring after exercise. Serum creatinine level was elevated, and he was admitted to our hospital with diagnosis of acute renal failure (ARF). He had experienced similar attacks at least 4 times, including the present episode, from the age of 22 years. After admission, the patient was managed only by resting, and remission was nearly attained in about 1 month. The renal biopsy specimen performed on day 15 showed findings of acute tubular necrosis, thickening of the tubular basement membrane, and interstitial fibrosis. After remission, the serum uric acid level was 0.7-0.8 mg/dl, fractional excretion of uric acid was 0.63, and the possibility of other diseases facilitating the excretion of uric acid was denied. Therefore, ARF associated with idiopathic renal hypouricemia was diagnosed. Since only mild responses were observed in a pyradinamide loading test and a benzbromarone loading test, the case was considered to be a presecretary reabsorption disorder type. Renal function tests showed the almost complete recovery of the glomerular filtration rate (GFR: 114 ml/min/1.73 m2), but the urine concentrating ability was markedly decreased (specific gravity 1.019 and osmolarity 516 mOsm/kgxH2O in Fishberg test). Past data from this patient indicated that this renal dysfunction had been persisting for ten years. We examined 9 patients with renal hypouricemia and focused on the differences between the two groups (with or without complications). Four patients had a history of exercise-induced ARF or calculus. The urine concentrating ability was significantly lower in these patients (group A) than in the other patients without complications (group B). The glomerular filtration rate in group A was within the normal range, but was lower than in group B. These results suggested the possibility that patients with renal hypouricemia with complications may have chronic renal dysfunction in the future.

Acute Kidney Injury↗
PubMed1999

Intranephron distribution and regulation of endothelin-converting enzyme-1 in cyclosporin A-induced acute renal failure in rats.

Endothelin-1 (ET-1) is thought to play a significant role in acute renal failure induced by cyclosporin A (CsA). The cDNA sequence encoding endothelin-converting enzyme-1 (ECE-1), which produces the active form of ET-1 from big ET-1, was recently reported. To elicit the role of ECE-1 in the glomerular and tubular dysfunction induced by CsA, the effects of CsA on mRNA and protein expression of ECE-1 in rat kidney and on mRNA expression of prepro-ET-1 and ET A- and B-type receptors in glomeruli were studied. ECE-1 mRNA was detected in glomeruli and in whole nephron segments. ECE-1 mRNA expression was downregulated in all nephron segments at 24 h after CsA injection. Protein levels were also downregulated in glomeruli and in the outer and inner medulla. CsA rapidly increased prepro-ET-1 mRNA expression in glomeruli at 30 to 60 min after injection; this rapid increase was followed by an increase in plasma ET-1 levels. These increases were followed by decreased expression of ECE-1, ET A-type receptor, and ET B-type receptor mRNA at 6 h after injection, and serum creatinine levels were increased at 24 h after CsA injection. It is suggested that downregulation of glomerular and tubular ECE-1 expression may be caused by increased ET-1 synthesis in CsA-induced acute renal failure.

Acute Kidney Injury↗
PubMed1999

[Kidney].

Kidney is one of the major target organ for angiotensin II (AT-II). The presence of three types of AT-II receptors, AT-II type 1, type 2, type 4 receptor (AT1, AT2, and AT4 receptor, respectively) were reported in kidney. AT1 receptor is the main type of receptor in kidney and mediates most of physiological effects of AT-II in kidney. The population of AT2 receptor is small in kidney. However, AT2 receptor also seems to play an important role for development and apoptosis in kidney. AT4 receptor is the receptor for angiotensin IV, but the physiological function is still unknown.

Humans↗
PubMed1997

mRNA distribution and membrane localization of the OAT-K1 organic anion transporter in rat renal tubules.

OAT-K1, a renal organic anion transporter, which mediates methotrexate uptake, was analyzed for mRNA distribution along microdissected nephron segments and the immunolocalization in isolated plasma membranes from rat kidney. By using a reverse transcription-coupled PCR, OAT-K1 mRNA was detected predominantly in the superficial and juxtamedullary proximal straight tubules. Western blotting with antiserum for OAT-K1 revealed that the transporter protein with the apparent molecular mass of 40 kDa was expressed exclusively in the brush-border membranes from rat kidney. These findings suggest that the OAT-K1 is localized in the brush-border membranes of the renal proximal straight tubules.

Amino Acid Sequence↗
PubMed1997

Quasi-steadiness approximation for the two-compartment solute kinetic model.

We analytically solved the equation of the variable volume, two-compartment solute kinetic model (TCSKM). From the solution, we constructed an expression of weekly concentration profiles developing in the patient's body by routine hemodialyses. Obtained formulas can be used to calculate Kt/V, solute reduction index (SRI), the solute generation rate (G) per unit distribution volume (V), and a mass transfer coefficient (MTC) between the two compartments. To estimate these parameters, the formulas only need three-point data during a dialysis, that is, pre-, one-hour, and post-dialysis solute concentrations instead of four that would otherwise be needed. A 48 hour data point is not required. The weekly concentration profiles can be easily calculated by the formulas. As examples of clinical applications, we calculated Kt/V, G/V, and SRI of urea, Cr, and uric acid using plasma data of 121 hemodialyzed patients. Then the results were compared with the single-compartment solute kinetic model (SCSKM). The obtained mean MTC/V values, that is, 1.08 (1/hr) for urea, 0.53 (1/hr) for Cr, and 1.11 (1/hr) for uric acid, were consistent with the previous works. SCSKM overestimated the mean G/V by 7.1%, 15.9%, and 10.0%, and the mean SRI by 6.7%, 18.6%, and 10.0%, for urea, Cr, and uric acid, respectively. The solute distribution volume ratio of TCSKM to SCSKM, (V)TCSKM/(V)SCSKM, depended on the value of MTC/V and the hemodialysis duration. Using pedometers, we measured the total number of steps the patients took during a week. We found that the total number of steps in a week was significantly correlated with the Cr generation rate (r = 0.285, P < 0.03), but that it was not significantly correlated with the other generation rates (r = 0.204, P > 0.09 for urea, and r = 0.209, P > 0.08 for uric acid). These data suggest that the Cr generation rate is related to the patient's physical activity. We conclude that the formulas can estimate an adequate dialysis prescription for the hemodialyzed patient.

Humans↗
PubMed1997

Microlocalization and effects of adrenomedullin in nephron segments and in mesangial cells of the rat.

We examined microlocalization of mRNA coding for adrenomedullin (AM), using reverse transcription-polymerase chain reaction (RT-PCR), and the effects of AM on adenosine 3',5'-cyclic monophosphate (cAMP) generation and water transport in microdissected rat nephron segments. We also examined intraglomerular site of the expression of AM and AM-stimulated cAMP generation in cultured rat mesangial cells (MC). RT-PCR demonstrated the signals for AM mRNA in glomerulus (Glm), cortical collecting duct (CCD), outer medullary collecting duct (OMCD), and inner medullary collecting duct (IMCD) but not in proximal convoluted tubule (PCT) or medullary thick ascending limb (MTAL). AM (10(-7) M) stimulated cAMP generation in Glm >> CCD = IMCD > OMCD but not in PCT or MTAL, which corresponded to the results of the expression of AM mRNA. AM (10(-8) M) slightly increased osmotic water permeability by 24% in perfused terminal IMCD. Northern blot analysis revealed high expression of AM mRNA in MC. AM (10(-7) M) stimulated cAMP generation in MC both in the presence and absence of fetal calf serum, suggesting that AM-dependent cAMP generation was evident both in cycling MC and in quiescent MC. AM may work as a diuretic peptide mainly by increasing glomerular filtration rate via cAMP in MC.

Adrenomedullin↗
PubMed1997

Endothelin converting enzyme-1 gene expression in the kidney of spontaneously hypertensive rats.

Abnormal renal handling of water and sodium is implicated in the pathogenesis of hypertension in spontaneously hypertensive rats (SHR). Alteration of renal endothelin-1 synthesis is also reported in SHR. Endothelin-1, a potent vasoconstrictor and regulator of sodium reabsorption in the nephron, has a pathophysiological potential in the development of hypertension. Because synthesis of bioactive endothelin-1 requires endothelin converting enzyme-1 (ECE-1), we investigated whether renal ECE-1 gene expression is altered in the kidney of SHR. Kidneys from both 4- and 12-week-old SHR and age-matched Wistar-Kyoto rats (WKY) were studied. ECE-1 mRNA in microdissected nephron segments was assessed by reverse transcription-competitive polymerase chain reaction, and ECE-1 protein level by Western blot. In 4-week-old SHR, ECE-1 mRNA was significantly increased in the proximal straight tubule, medullary thick ascending limb, cortical thick ascending limb, and inner medullary collecting duct. ECE-1 protein level was increased in both the outer and inner medulla. In 12-week-old SHR, ECE-1 gene expression was significantly increased in the proximal straight tubule, medullary thick ascending limb, and also in the glomeruli. Glomerular preproendothelin-1 mRNA expression was not different between the two strains at both 4 and 12 weeks. We conclude that high ECE-1 gene expression in the nephron, via increase of endothelin-1 synthesis, may promote sodium retention that contributes to the development and/or maintenance of hypertension in SHR.

Aging↗
PubMed1997

Expression of PDGF and PDGF receptor mRNA in glomeruli in IgA nephropathy.

This study investigated the mRNA expression of the platelet-derived growth factor (PDGF) A-chain and B-chain and PDGF-beta receptor in glomeruli of 15 immunoglobulin A (IgA) nephropathy kidneys and those with minimal-change lesion (N = 7), membranous nephropathy (N = 3), and focal segmental glomerulonephritis (N = 5), by using competitive RT-PCR methods. The level of PDGF B-chain and beta receptor mRNA expression in IgA nephropathy was significantly higher than in the other forms of glomerulonephritis, but mRNA expressions of PDGF A-chain were not significantly different. Significant correlations were observed between the urinary protein level and the mRNA level of PDGF-beta receptor expression and PDGF B-chain expression, and between the serum creatinine level and the mRNA level of PDGF-beta receptor expression. The PDGF B-chain and beta-receptor may be upregulated and accelerate cell proliferation in a paracrine or autocrine manner and may play a role in the pathogenesis of IgA nephropathy.

Becaplermin↗
PubMed1997

Effects of quinapril hydrochloride in patients with essential hypertension and impaired renal function.

The short-term effects of administration of an angiotensin-converting enzyme (ACE) inhibitor, quinapril hydrochloride (quinapril) (5-10 mg/day), for 12 weeks on blood pressure and renal function were evaluated in 8 patients (60.5 +/- 7.3 years old, mean +/- SD) with mild to moderate essential hypertension and mild impairment of renal function due to nephrosclerosis. Systolic blood pressure and diastolic blood pressure were significantly reduced from 163.0 +/- 4.0 to 132.3 +/- 17.6 mmHg (p < 0.01) and from 98.3 +/- 4.6 to 81.5 +/- 6.4 mmHg (p < 0.001), respectively, before to after treatment. Both renal plasma flow (RPF) and glomerular filtration rate (GFR) were significantly increased in all patients, from 203.9 +/- 33.3 to 245.4 +/- 36.7 ml/min/1.73 m2 (p < 0.01), and from 43.4 +/- 6.4 to 53.5 +/- 4.6 ml/min/1.73 m2 (p < 0.05), respectively. Short-term quinapril administration was beneficial to renal function in patients with essential hypertension and impaired renal function.

Aged↗
PubMed1996

Role of urinary arginine vasopressin in the sodium excretion in patients with chronic renal failure.

Patients with chronic renal failure show almost equal levels of sodium excreted in the urine as healthy subjects through an increase of the fractional excretion sodium (FE(Na)). The mechanisms of this adaptation, however, are unknown. Recently, urinary arginine vasopressin (AVP) has been shown to inhibit the antidiuretic action of plasma AVP in the collecting ducts of rabbits and rats. In this article, the roles of plasma and urinary AVP are examined with other hormones in the sodium excretion of 57 patients with chronic renal disease. The fractional excretion of AVP, plasma atrial natriuretic peptide (ANP) and endothelin-1 (ET-1), urinary ET-1, and FE(ET-1) correlated with the decrease of creatinine clearance (Ccr). Multiple and stepwise regression analyses showed that FE(AVP) is the major dependent determinant for FE(Na) (adjusted r2 = 0.78). These results suggest that the increase of AVP excretion per remaining nephron could be a cause of the increase of FE(Na) in patients with renal failure. Although plasma AVP works as an antidiuretic hormone, urinary AVP serves as an intrinsic diuretic, especially in patients with chronic renal failure.

Adolescent↗
PubMed1996

[Na+/K+/2Cl- cotransport protein, Na+/Cl- cotransport protein].

The bumetanide-sensitive Na+/K+/2Cl- cotransporter and the thiazide-sensitive Na+/Cl- cotransporter are present in a wide variety of tissues, and appear to serve physiological cell functions such as volume control, particularly the phenomenon known as regulatory volume control, and net secretion or absorption of salt. The recent cDNA cloning of these two cotransporters suggests that they are members of the same new family, because they exhibit a topology featuring 12 potential membrane-spanning helices flanked by large hydrophilic domains at the NH2- and COOH-termini. The transporters are regulated by phosphorylation directly via protein kinase and dephosphorylation via phosphatase, and perhaps secondary to decrease of Cl concentration in the cell by activated Cl channel.

Animals↗