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Biomedical subjects

H Nonoguchi

Publications and source records attributed to H Nonoguchi.

At least 55 records · Page 3Linked to original sources
PubMed1993

PCR localization of angiotensin II receptor and angiotensinogen mRNAs in rat kidney.

Recent studies revealed that angiotensin II (Ang II) interacts with two pharmacologically different subtypes of cell surface receptors. Type I Ang II (AT1) receptor is characterized by signal transduction mediated through G protein and phospholipase C. In this study, the micro-localization of mRNAs coding for AT1 receptor and angiotensinogen was carried out in the rat kidney, using an assay of reverse transcription and polymerase chain reaction (RT-PCR) in individual microdissected renal tubule segments along the nephron, glomeruli, vasa recta bundle, and arcuate arteries. Large signals for AT1 receptor were detected in the glomerulus, proximal convoluted tubule (PCT), proximal straight tubule (PST), cortical collecting duct, and vascular system. Small signals were also seen in medullary thick ascending limb, outer medullary collecting duct, and inner medullary collecting duct (IMCD). Angiotensinogen mRNA is expressed largely in PCT, PST, and a small amount in glomerulus and vasa recta. Our data demonstrate that Ang II could be produced locally in proximal tubule and vasa recta bundle, and that the AT1 receptor was widely distributed not only in the glomerulus and vessels but also in tubules from PCT to IMCD.

Angiotensin II↗
PubMed1993

Expression of endothelin-3 mRNA along rat nephron segments using polymerase chain reaction.

Endothelin (ET) is now known to be a family of three distinct peptides. Although many reports have studied the renal action of ET-1, comparatively little is known concerning ET-3. We previously reported that ET-1 mRNA is expressed in glomerulus (Glm) and inner medullary collecting duct (IMCD). In this study, microlocalization of mRNA coding ET-3 was carried out in the rat kidney using a reverse transcription and polymerase chain reaction (RT-PCR) assay of individual microdissected renal tubule segments along the nephron, Glm, vasa recta bundle, and arcuate arteries. Large signals for ET-3 PCR product were detected in proximal convoluted and straight tubules, cortical collecting duct, and outer medullary collecting duct. Glm, IMCD, and vasa recta bundle also expressed relatively large amounts of ET-3 mRNA. Small signals were found in medullary thick ascending limb, inner medullary thin limb, and arcuate artery. We detected ET-3 protein in tubule suspensions from cortex, outer medulla, and inner medulla of rat kidney. Furthermore, incubation with TGF-beta did not change ET-3 PCR signal, whereas ET-1 PCR signal was increased significantly by exposure to TGF-beta in Glm and IMCD. Thus, ET-3 and ET-1 are distributed differently along the nephron and are regulated in different manners. This suggests that ET-3 and ET-1 may affect kidney functions in different ways.

Animals↗
PubMed1993

Effect of hyperosmolality on production and mRNA expression of ET-1 in inner medullary collecting duct.

The effects of hyperosmolality on the production and mRNA expression of endothelin-1 (ET-1) in inner medullary collecting duct (IMCD) were examined in the present study. Osmolality in incubation media was changed from 290 to 490 or 690 mosmol/kgH2O by adding NaCl, urea, mannitol, or raffinose. A preliminary experiment was carried out using tubule suspension from the inner medulla. Hyperosmolality by NaCl stimulated ET-1 accumulation in rats (from 323.5 +/- 76.3 to 478.0 +/- 108.4 and 573.7 +/- 47.8 pg.mg protein-1 x 24 h-1 in 290, 490, and 690 mosmol/kgH2O, respectively) and rabbits. In contrast, hyperosmolality by urea markedly decreased ET-1 accumulation and hyperosmolality by mannitol showed no effect on it. We next examined whether hyperosmolality changes ET-1 mRNA. After incubation in isotonic or hypertonic solution for 6 h, ET-1 mRNA was determined using reverse transcription and polymerase chain reaction (PCR) in microdissected IMCD and glomerulus. Hyperosmolality by NaCl and raffinose significantly increased the PCR products of ET-1 mRNA in IMCD, whereas mannitol did not. The stimulatory effect of hyperosmolality by NaCl on ET-1 mRNA expression was not observed in glomerulus. Our data suggested a stimulatory effect of hyperosmolality on production and mRNA expression of ET-1 in IMCD but not in glomerulus.

Animals↗
PubMed1993

Effects of ET-1 on water and chloride transport in cortical collecting ducts of the rat.

Endothelin-1 (ET-1) is known as a vasoconstrictor peptide. However, recent reports suggested the effects on the transport of renal tubule. We previously reported that ET-1 inhibited arginine vasopressin (AVP)-dependent adenosine 3',5'-cyclic monophosphate in rat collecting ducts. Physiologically, ET-1 reversibly and significantly inhibited AVP-stimulated water permeability in inner medullary collecting duct (IMCD). We therefore investigated the effects on water and electrolyte transport in rat cortical collecting ducts (CCD), where Na and Cl are actively reabsorbed more than in IMCD. Pathogen-free male Sprague-Dawley rats weighing 80-120 g were used after treatment with deoxycorticosterone pivalate for 1-2 wk. Isolated CCD were microperfused in vitro. The Cl concentration was measured by a continuous-flow ultra-microcolorimeter, and the raffinose concentration was measured as a volume marker by a continuous-flow ultra-microfluorometer. In the presence of 10(-9) M AVP, 10(-8) M ET-1 significantly inhibited fluid absorption (nl.mm-1 x min-1) from 0.25 +/- 0.02 to 0.15 +/- 0.05 (mean +/- SE, n = 6, P < 0.01), Cl absorption (pmol.mm-1 x min-1) from 30. 6 +/- 2.8 to 14.9 +/- 4.0 (P < 0.01), and potential difference (mV) from -5.4 +/- 1.3 to -4.0 +/- 1.2 (P < 0.01). Similar results were obtained in the lower concentration of 10(-10) M AVP and 10(-10) M ET-1. As for the osmotic water permeability (microns/s), 10(-8) M ET-1 significantly inhibited this from 320.1 +/- 50.9 to 202.1 +/- 42.2 (n = 7, P < 0.01) in the presence of 10(-9) M AVP.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Different localization and regulation of two types of vasopressin receptor messenger RNA in microdissected rat nephron segments using reverse transcription polymerase chain reaction.

Recent studies have revealed that arginine vasopressin (AVP) has at least two types of receptors in the kidney: V1a receptor and V2 receptor. In this study, microlocalization of mRNA coding for V1a and V2 receptors was carried out in the rat kidney using a reverse transcription and polymerase chain reaction. Large signals for V1a receptor PCR product were detected in the glomerulus, initial cortical collecting duct, cortical collecting duct, outer medullary collecting duct, inner medullary collecting duct, and arcuate artery. Small but detectable signals were found in proximal convoluted and straight tubules, inner medullary thin limbs, and medullary thick ascending limbs. Large signals for V2 receptor mRNA were detected in the cortical collecting duct, outer medullary collecting duct, and inner medullary collecting duct. Small signals for V2 receptor were found in the inner medullary thick limbs, medullary thick ascending limbs, and initial cortical collecting duct. Next, we investigated V1a and V2 receptor mRNA regulation in the dehydrated state. During a 72-h water restriction state, the plasma AVP level increased and V2 receptor mRNA decreased in collecting ducts. In contrast, V1a receptor mRNA did not change significantly. Thus, the two AVP receptor subtypes are distributed differently along the nephron, and these mRNAs are regulated differently in the dehydrated state.

Animals↗
PubMed1993

Effect of urodilatin on cGMP accumulation in the kidney.

Urodilatin is found in the urine and is thought to be produced in the kidney. The effect of urodilatin on cGMP accumulation in the kidney was investigated. cGMP accumulation by urodilatin and atrial natriuretic peptide (ANP) were compared with tubule suspensions from renal cortex, outer medulla, inner medulla, and microdissected nephron segments. Urodilatin-stimulated cGMP accumulation was higher in tubule suspensions from the inner medulla than in those from the cortex and outer medulla. The highest accumulation stimulated by 10(-6) M urodilatin among nephron segments was observed in glomeruli and inner medullary collecting ducts (IMCD). Small accumulations were seen in proximal convoluted tubules and medullary thick ascending limbs. Urodilatin-stimulated cGMP accumulation was almost equal to that stimulated by the same concentrations of ANP in these nephron segments. Urodilatin (10(-8) M) did not stimulate cGMP accumulation in glomeruli, but it stimulated cGMP accumulation in IMCD by threefold. This pattern was quite similar to that with ANP. It was concluded that urodilatin has a similar ability to ANP in stimulating cGMP synthesis and that the main target sites are glomeruli and IMCD.

Animals↗
PubMed1992

Renal effects of alacepril in essential hypertension.

Short-term effects of alacepril, an angiotensin-converting enzyme inhibitor (ACEI), on renal function and hemodynamics were investigated in 10 hypertensive subjects (aged 55.7 +/- 9.5 years, mean +/- SD). Renal plasma flow (RPF) and glomerular filtration rate (GFR) were examined before and after 12-week administration of alacepril, by [131I]hippuran and [99mTc]DTPA, respectively. Alacepril (50 mg/day) caused a significant decrease in both systolic and diastolic blood pressure (SBP and DBP, from 161 +/- 8 to 140 +/- 10 mm Hg and from 100 +/- 3 to 90 +/- 5 mm Hg, respectively). Alacepril increased GFR (from 63.4 +/- 22.2 to 69.1 +/- 22.1 ml/min/1.73 m2, p less than 0.05) without changing RPF (from 438 +/- 194 to 432 +/- 148 ml/min/1.73 m2, p greater than 0.05). Serum creatinine and electrolytes were not changed by alacepril administration. These data show that short-term alacepril administration improves renal function, probably owing to relaxation of renal vasoconstriction.

Adult↗
PubMed1992

Hormone and autacoid regulation of cAMP production in rat IMCD subsegments.

The inner medullary collecting duct (IMCD) of the rat consists of two structurally and functionally distinct segments, i.e., the initial and the terminal IMCD. To identify factors that may regulate the transport function in the IMCD segments, we assessed whether catecholamines, carbachol, prostaglandin E2 (PGE2), bradykinin, glucagon, calcitonin, parathyroid hormone, or epidermal growth factor affects adenosine 3',5'-cyclic monophosphate (cAMP) production in microdissected tubules in the presence and absence of arginine vasopressin (AVP, 0.1 nM). All experiments were performed in the presence of 3-isobutyl-1-methylxanthine, and cAMP was measured by radioimmunoassay. Epinephrine (greater than or equal to 50 nM) and clonidine (greater than or equal to 1 microM) markedly decreased AVP-induced cAMP levels in both IMCD segments. However, phenylephrine did not show an effect. The inhibitory effect of epinephrine was blocked by yohimbine (50 nM) but not by prazosin (50 nM). In isolated perfused terminal IMCDs, epinephrine inhibited AVP-stimulated urea permeability. Isoproterenol (1 microM), in the absence of AVP, caused a significant increase in cAMP level only in the initial IMCD. Propranolol (1 microM) inhibited this isoproterenol effect, but atenolol did not. Dopamine (less than or equal to 1 microM) had no effect on cAMP levels in either IMCD segment. Carbachol, PGE2, and the various peptide hormones had no effect on cAMP levels (+/- AVP) in either IMCD segment. We conclude that an adrenergic beta 2-receptor is present only in the initial IMCD, where its occupation increases cAMP production. We conclude also that an adrenergic alpha 2-receptor is present in both IMCD segments, where its occupation inhibits AVP-induced cAMP production.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Different localization of two types of endothelin receptor mRNA in microdissected rat nephron segments using reverse transcription and polymerase chain reaction assay.

Recent studies have revealed that endothelins (ETs) have at least two types of receptors. One receptor has high affinity to ET-1 and ET-2 and low affinity to ET-3 (A type). The other receptor binds almost equally to ET-1, ET-2, and ET-3 (B type). In this study, microlocalization of mRNA coding for the A-type and B-type ET receptors was carried out in the rat kidney using a reverse transcription and polymerase chain reaction assay of individual microdissected renal tubule segments along the nephron, glomeruli, vasa recta bundle, and arcuate arteries. Large signals for the B-type receptor polymerase chain reaction product were detected in the initial and terminal inner medullary collecting duct and the glomerulus, while small signals were found in the cortical collecting duct and outer medullary collecting duct, vasa recta bundle, and arcuate artery. In contrast, A-type receptor mRNA was detected only in the glomerulus, vasa recta bundle, and arcuate artery. Thus, the two ET receptor subtypes are distributed differently along the nephron. This suggests that the two types of receptors and ET families may affect kidney functioning in different ways.

Animals↗
PubMed1992

Effects of atrial natriuretic peptide and vasopressin on chloride transport in long- and short-looped medullary thick ascending limbs.

Recent studies have suggested a selective effect of atrial natriuretic peptide (ANP) in regulating NaCl reabsorption in juxtamedullary nephrons. We examined (a) functional differences between medullary thick ascending limbs from long and short loops of Henle (lMAL and sMAL, respectively) and (b) the interaction of ANP and arginine vasopressin (AVP) on Cl- transport (JCl) in these two segments. AVP-, glucagon-, and calcitonin-stimulated cAMP accumulation was higher in lMAL than in sMAL. 10(-10) M AVP increased JCl in lMAL but not in sMAL. ANP-stimulated cGMP production was higher in lMAL than in sMAL. 10(-10) and 10(-8) M ANP inhibited AVP-stimulated JCl in lMAL by 26-30% (from 70.3 +/- 11.4 to 51.7 +/- 13.6 pmol/mm per min and from 88.1 +/- 10.1 to 61.8 +/- 11.7 pmol/mm per min, respectively), and this effect was mimicked by 10(-5) to 10(-4) M cGMP. This effect of ANP in lMAL could account for a large part of the ANP-induced natriuresis and diuresis in vivo, in that the rate of NaCl reabsorption in MAL is the largest among distal nephron segments, providing the chemical potential energy for the renal countercurrent multiplication system.

Animals↗
PubMed1992

Polymerase chain reaction localization of constitutive nitric oxide synthase and soluble guanylate cyclase messenger RNAs in microdissected rat nephron segments.

Stimulation of the release of nitric oxide (NO) in the kidney has been shown to result in renal hemodynamic changes and natriuresis. NO is a potent stimulator of soluble guanylate cyclase, leading to an increase of cyclic GMP. The precise localization of NO synthase and soluble guanylate cyclase in the renal structure is not known. In this study, the microlocalization of mRNAs coding for constitutive NO synthase and soluble guanylate cyclase was carried out in the rat kidney, using an assay of reverse transcription and polymerase chain reaction in individual microdissected renal tubule segments along the nephron, glomeruli, vasa recta bundle, and arcuate arteries. A large signal for constitutive NO synthase was detected in inner medullary collecting duct. Small signals were detected in inner medullary thin limb, cortical collecting duct, outer medullary collecting duct, glomerulus, vasa recta, and arcuate artery. Soluble guanylate cyclase mRNA is expressed largely in glomerulus, proximal convoluted tubule, proximal straight tubule, and cortical collecting duct, and in small amounts in medullary thick ascending limb, inner medullary thin limb, outer medullary collecting duct, inner medullary collecting duct, and the vascular system. Our data demonstrate that NO can be produced locally in the kidney, and that soluble guanylate cyclase is widely distributed in glomerulus, renal tubules, and the vascular system.

Amino Acid Oxidoreductases↗
PubMed1992

Messenger RNA expression and synthesis of endothelin-1 along rat nephron segments.

The kidney both produces and responds to endothelin. We examined the production and the expression of mRNA of endothelin-1 (ET-1) in tubule suspensions and microdissected nephron segments. ET-1 production was measured by RIA using an ET-1-specific antibody. We applied the reverse transcription and polymerase chain reaction (PCR) technique to detect ET-1 mRNA along the nephron segments. Stimulation of ET-1 production was observed in the presence of FCS and transforming growth factor-beta (TGF-beta) in inner medullary tubules but not in cortical or outer medullary tubule suspensions. Among dissected nephron segments, ET-1 production was observed in glomeruli and inner medullary collecting ducts (IMCD), whereas it was negligible in proximal convoluted tubules (PCT) and medullary thick ascending limbs (MAL). In addition, the PCR product of ET-1 mRNA was also higher in glomeruli and IMCD, whereas it was undetectable in PCT and MAL. Furthermore, FCS and TGF-beta increased ET-1 mRNA in microdissected glomeruli and IMCD. These data clearly demonstrated that the production sites of ET-1 are glomeruli and IMCD among the nephron segments. ET-1 is an autocrine factor in these sites.

Animals↗
PubMed1991

Endothelin-1 inhibits AVP-stimulated osmotic water permeability in rat inner medullary collecting duct.

Endothelin causes diuresis despite an accompanying decrease in glomerular filtration rate and renal plasma flow. Binding sites for endothelin are located not only in glomeruli but also in the inner medulla, possibly in inner medullary collecting ducts (IMCD). To determine whether endothelin has a direct tubular effect, effects of endothelin on water and urea transport were investigated using isolated microperfusion of rat IMCD segments in vitro. Endothelin, at 10(-10) and 10(-8) M, reversibly inhibited 10(-11) M arginine vasopressin (AVP)-stimulated osmotic water permeability (Pf) by 18 and 24%, respectively. Endothelin (10(-8) M) also inhibited Pf by 23% in the presence of a much higher dose of AVP (10(-9) M), whereas endothelin had no effect on Pf in the absence of AVP. On the other hand, 10(-8) M endothelin did not inhibit Pf stimulated by 10(-3) M dibutyryl adenosine 3',5'-cyclic monophosphate (cAMP). Endothelin had no inhibitory effect on AVP-stimulated urea permeability. These data suggest that endothelin can cause diuresis by inhibiting AVP-stimulated Pf in IMCD and that the site of action is previous to cAMP generation.

Animals↗