Biomedical subjects

F Marumo

Publications and source records attributed to F Marumo.

At least 451 records · Page 25Linked to original sources

PubMed1992

Anaerobic metabolism as an indicator of aerobic function during exercise in cardiac patients.

To determine whether patients with heart disease depend more than normal subjects on anaerobic metabolism to perform the same level of exercise, the anaerobic threshold, slope of the increase in carbon dioxide output with respect to oxygen uptake (delta VCO2/delta VO2) and the slope of the increase in oxygen uptake with respect to the increase in work rate (delta VO2/delta WR) both below and above the anaerobic threshold during exercise were evaluated. A total of 106 patients with chronic heart disease and 42 healthy subjects performed a symptom-limited incremental exercise test in a ramp pattern on a cycle ergometer. Peak oxygen uptake was significantly lower in the patients with heart disease than in the normal subjects. The anaerobic threshold, which was 20 +/- 4.6 ml/min per kg in normal subjects, decreased significantly with progressing severity of functional class: 16 +/- 2.4, 14.1 +/- 2.5 and 11.3 +/- 1.5 ml/min per kg, respectively, in patients in class I, class II and class III. The slope of delta VO2/delta WR, which represents the degree of aerobic metabolism, was also decreased both below and above the anaerobic threshold with increasing severity of heart disease. delta VCO2/delta VO2 below the anaerobic threshold was approximately 0.9 (p = NS between normal subjects and patients). However, delta VCO2/delta VO2 above the anaerobic threshold became steeper with increasing severity of heart disease: 1.37 +/- 0.17 in normal subjects versus 1.55 +/- 0.24, 1.67 +/- 0.3 and 1.8 +/- 0.35 respectively, in patients in functional class I, class II and class III.(ABSTRACT TRUNCATED AT 250 WORDS)

Aerobiosis↗

PubMed1992

Regulation of endothelin-1 production in cultured rat mesangial cells.

We investigated the regulatory mechanisms of endothelin (ET)-1 production in cultured rat mesangial cells (MC), with a special focus on the roles of protein kinase A (PKA)- and protein kinase C (PKC)-mediated signaling systems. Vasoactive agents and growth promoting factors, including platelet-derived growth factor, vasopressin and thrombin, which act through receptors coupled to the phospholipase C-mediated signaling system, as well as phorbol ester and fetal calf serum stimulated ET-1 production. This effect was attenuated in PKC-depleted or H-7 (a PKC inhibitor) treated MC. On the other hand, an increase in intracellular cyclic AMP by forskolin or beta-adrenergic agonist, isoproterenol, which act as anti-mitogenic agents, inhibited serum-stimulated ET-1 production. In addition this effect was mimicked by the addition of 8-bromo-cyclic AMP to the medium. The effect of isoproterenol was abolished by propranolol. H-8, a PKA inhibitor, attenuated the inhibitory effect of forskolin. These findings suggest that ET-1 production in MC is regulated by interaction of both positive and negative signals mediated by PKC- and PKA-dependent mechanisms.

Animals↗

PubMed1992

Combined class I antiarrhythmic agents have differential effects on tonic and use dependent block of maximum rate of depolarisation of action potentials in guinea pig cardiac muscle.

OBJECTIVE: The aim was to study the difference between tonic and use dependent block of the cardiac sodium channel produced by the combined application of the same subclass of antiarrhythmic agents (class Ia or Ib). METHODS: Conventional glass microelectrode technique was used to record the maximum rate of depolarisation (dV/dtmax) of action potentials reflecting sodium channel availability, before and after the combined application of quinidine plus disopyramide, aprindine plus lignocaine, aprindine plus mexiletine, and lignocaine plus mexiletine. Guinea pig papillary muscles (n = 4-8 per experiment) were used for the study. RESULTS: All combinations increased tonic block additively compared to use of a single drug. On the other hand, use dependent block was increased by the combination of quinidine 10 microM plus disopyramide 30 microM compared to a single drug, and was not changed by lignocaine 50 microM plus mexiletine 20 microM, whereas it was decreased by aprindine 3 microM plus lignocaine 50 microM or mexiletine 20 microM. When concentrations of mexiletine and lignocaine were increased, both tonic and use dependent block in a single drug were increased dose dependently, whereas the combination produced an additive increase in tonic block but no change in use dependent block compared to a single drug. CONCLUSIONS: The results suggested that the binding and unbinding process of the drug to produce tonic block was different from that to produce use dependent block, and that combination of different drugs produced diverse effects on use dependent block even though state dependent affinity of individual drugs seemed similar. These two factors must be born in mind in evaluating the combination therapy.

Action Potentials↗

PubMed1992

Structure of the bovine endothelin-B receptor gene and its tissue-specific expression revealed by northern analysis.

We have isolated and characterized the gene encoding the bovine endothelin (ET) receptor ETB with seven putative membrane-spanning domains. The gene exists as a single copy of the bovine genome and extends over 36 kilobases. The coding region is divided into seven exons separated by six introns; the first exon encodes the first and second transmembrane domains and each of the following transmembrane domains is encoded by a separate exon. The 5' region of the transcript was examined by the ribonuclease protection analysis; multiple start sites were deduced with no apparent "TATA" box in the expected upstream region. Northern blot analysis demonstrated a widespread but tissue-specific distribution of the ETB receptor in bovine tissues.

Amino Acid Sequence↗

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

Effect of long-term carvedilol therapy on renal function in essential hypertension.

We assessed the long-term effects of carvedilol on renal function in 10 patients with mild-to-moderate essential hypertension. After a 2- to 4-week placebo run-in period, all patients received 5 mg carvedilol once daily. If the effect was insufficient, the dosage was successively increased to 10 or 20 mg once daily. The mean +/- SEM duration of treatment was 17.3 +/- 1.0 weeks, and the final mean daily dosage was 13.5 +/- 2.2 mg/day. With treatment, systolic and diastolic blood pressures decreased significantly from 159.7 +/- 1.3 to 140.5 +/- 3.2 mm Hg (p less than 0.001) and from 98.3 +/- 1.0 to 88.2 +/- 2.7 mm Hg (p less than 0.001), respectively. Carvedilol did not cause significant changes in glomerular filtration rate, effective renal plasma flow, blood urea nitrogen, or serum creatinine. Renal vascular resistance decreased significantly from 12.7 +/- 1.4 to 11.2 +/- 1.2 dyne.s.cm-5/1.48 m2 x 10(3) (p less than 0.05). Thus, long-term carvedilol therapy was effective in reducing blood pressure in essential hypertension without causing impairment of renal function.

Administration, Oral↗

PubMed1992

L-arginine infusion induces hypotension and diuresis/natriuresis with concomitant increased urinary excretion of nitrite/nitrate and cyclic GMP in humans.

1. The vascular endothelium produces endothelium-derived relaxing factor (EDRF) or nitric oxide (NO), which exerts vasodilation through cyclic guanosine monophosphate (cGMP) as a second messenger. To determine whether EDRF has any vasodilating and natriuretic action in man, the present study examined the effects of L-arginine (L-Arg), a substrate for NO, on the responses of mean blood pressure (MBP) and heart rate (HR); plasma concentrations of cGMP, atrial natriuretic factor (ANF) and nitrite/nitrate (NOx); urinary excretion of sodium, cGMP and NOx; and urinary flow in eight normal male subjects. These parameters were compared with those following saline infusion in the same subjects. Clearance of para-aminohippuric acid (PAH) and inulin was studied in five normal subjects. 2. Infusion of L-Arg (30 g) caused a significant fall in MBP (-8 mmHg) with a concomitant rise in HR (10 beats/min), while saline infusion had no effects on these parameters. 3. Neither L-Arg nor saline infusion caused appreciable changes in plasma concentrations of ANF or NOx. Plasma cGMP concentrations increased significantly during (1.7-fold) and after (1.9-fold) L-Arg infusion, but only slightly (1.3-fold) during saline infusion. 4. Urine flow increased more remarkably following L-Arg infusion than that following saline infusion. Remarkable increases in urinary excretion of sodium and fractional excretion of sodium were observed after L-Arg infusion compared with those after saline infusion. Natriuresis was associated with enhanced urinary excretion of cGMP and Nox. Urinary Nox excretion showed positive correlations with urinary flow (r = 0.69, P less than 0.001) and with urinary cGMP excretion (r = 0.60, P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1992

Changes of circulating atrial natriuretic peptide and antidiuretic hormone in obstructive sleep apnea syndrome.

Patients with obstructive sleep apnea (OSA) syndrome are known to exhibit nocturnal natriuresis/diuresis. We studied plasma and urinary levels of atrial natriuretic peptide (ANP), a potent natriuretic hormone released from the heart, and plasma antidiuretic hormone (ADH) levels in patients with OSA during awake and sleeping periods, to compare with those of normal subjects. Seven patients with OSA and 6 normal subjects were studied. Arterial blood samples were drawn during the awake and the sleeping period, while in patients with OSA, blood samples were obtained during the apneic period. Urine samples were collected over two 12-hour periods (9 a.m.-9 p.m. and 9 p.m.-9 a.m.) In patients with OSA, plasma ANP as well as urinary ANP excretion increased during the apneic period compared with the awake period. There was a significant negative correlation between plasma levels of ANP and ADH in patients with OSA. On the other hand, normal subjects had no apparent differences in plasma and urinary ANP levels between the two periods. It is suggested that nocturnal increase in ANP and decrease in ADH are responsible for the nocturnal diuresis and natriuresis associated with OSA.

Adult↗

PubMed1992

Cardiac output-O2 uptake relation during incremental exercise in patients with previous myocardial infarction.

BACKGROUND: The cardiac output-O2 uptake (VO2) relation, which is thought to be linear and predictable in normal humans, has not been clarified in cardiac patients. We evaluated the relation between cardiac output and VO2 during the incremental exercise test in patients with previous myocardial infarction. METHODS AND RESULTS: Twenty-two patients (age, 58.1 +/- 8.0 years) with previous myocardial infarction performed a symptom-limited exercise test on a cycle ergometer. VO2 was calculated from the expired gas analysis, and cardiac output was measured by a computerized cadmium telluride detector every 10 seconds during exercise. The ratio of increase in VO2 to the increase in work rate (delta VO2/delta WR) below and above the anaerobic threshold (AT) was 11.1 +/- 3.6 and 11.1 +/- 2.9 ml/min/W, respectively, showing no significant difference. However, the ratio of increase in cardiac output to increase in work rate (delta CO/delta WR) below the AT was 50.1 +/- 26.6 ml/min/W and was significantly decreased to 11.8 +/- 25.3 ml/min/W above the AT (p = 0.0002). The decreased delta CO/delta WR above the AT primarily would be due to silent myocardial ischemia produced by exercise, as there was the presence of 201Tl redistribution in 15 of 16 patients in whom myocardial 201Tl scintigraphy with dipyridamole or exercise stress testing was evaluated. delta CO/delta VO2, which has been reported to be approximately 5.5 in normal subjects, was only 4.4 +/- 2.6 at work rates below the AT and was decreased to 1.1 +/- 2.3 at work rates above the AT. CONCLUSIONS: The relation between cardiac output and VO2 during exercise in patients with previous myocardial infarction differs profoundly from that reported in normal subjects. These findings must be considered when we noninvasively estimate the change in cardiac output during exercise by obtaining VO2 in patients with coronary artery disease.

Adult↗

PubMed1992

Combined use of time and frequency domain variables in signal-averaged ECG as a predictor of inducible sustained monomorphic ventricular tachycardia in myocardial infarction.

BACKGROUND: Time and frequency domain analyses of signal-averaged ECG (SAECG) have several individual limitations, and the results of the two methods sometimes vary considerably. The purpose of this study was to determine whether the combined use of time and frequency domain variables facilitates identification of patients who will have ventricular tachycardia (VT) induced during programmed ventricular stimulation (PVS). METHODS AND RESULTS: Nine myocardial infarction (MI) patients with clinically documented sustained monomorphic VT (SMVT), 40 MI patients without clinical VT, and 30 normal healthy control subjects were evaluated. PVS using three extrastimuli and SAECG recording were performed in the MI patients on day 36 +/- 4 after infarction. Of 40 MI patients, SMVT was inducible in 14, sustained polymorphic VT in three, nonsustained monomorphic VT in three, nonsustained polymorphic VT in two, and no inducible arrhythmia was obtained in 18. There were significant differences between MI patients with inducible SMVT and without inducible SMVT in the following SAECG variables: filtered QRS durations (high-pass filter setting, 25, 40, and 80 Hz); low-amplitude signal durations (LAS) under 10, 20, 30, and 40 microV (high-pass filter setting, 40 and 80 Hz); root-mean-square voltages (RMS) of the terminal 20, 30, 40, 50, and 60 msec (high-pass filter setting, 40 and 80 Hz); area ratio (area 20-50 Hz/area 0-20 Hz x 10(5)) of a 120-msec sampling interval starting 20 msec before QRS offset; factor of normality on lead X; and minimum value of the variables on lead X, Y, or Z. Stepwise logistic regression analysis selected only LAS under 30 microV (high-pass filter setting, 80 Hz) and area ratio as independent predictors of inducible SMVT. With these two variables, the predicted probability of inducible SMVT [p(VT)] was expressed as p(VT) = 1/[1+exp (6.2-0.11 LAS-0.01 area ratio)]. This function had 93% sensitivity, 81% specificity, 72% positive predictive value, 95% negative predictive value, and 85% predictive accuracy with greater than or equal to 0.3 as the criterion of a positive test. CONCLUSIONS: The combined use of time and frequency domain analysis of SAECG can enhance the accuracy of this technique as a screening test for results of PVS in MI patients without clinical VT.

Aged↗

PubMed1992

Myocardial uptake of 111In monoclonal antimyosin Fab in detecting doxorubicin cardiotoxicity in rats. Morphological and hemodynamic findings.

BACKGROUND: The therapeutic value of doxorubicin (DOX) is limited by its cardiotoxicity, which is dose dependent. To improve the detection of such myocardial damage, this study was designed to determine whether the 111In antimyosin antibody Fab could serve as a marker for cardiotoxicity in treated versus control rats on the basis of comparative morphological and hemodynamic findings. METHODS AND RESULTS: DOX was administered by intravenous injection to rats at a dose of 3 mg.kg-1.week-1 for 5 weeks. Three weeks after the final injection, an intravenous dose of 111In antimyosin, 740 kBq (20 microCi), was administered, and tissue distribution of the radioisotope (percent kilogram dose per gram) was assessed in 48 hours. Myocardial uptake of radioactivity by both ventricles was more prominent in the DOX-treated rats than in control rats (p < 0.001). The heart-to-blood and heart-to-lung uptake ratios were markedly higher in the treated rats than in controls (p < 0.001). As the severity of the myocardial damage increased, there was a progressive increase in myocardial uptake. There was a strong correlation between the severity of myocardial damage and the ventricular end-diastolic pressure (r = 0.84 and r = 0.83 in the left and right ventricles, respectively). On microscopic immunoautoradiography of the DOX-treated heart, there was a specific immunolocalization of the radiotracer in the injured myocytes but no radioactivity in the control myocytes. CONCLUSIONS: 111In antimyosin antibody appears to be a useful immunoradiotracer in detecting cardiac damage induced by DOX administration and in assessing the severity of cardiotoxicity. These data reinforce the clinical observation that myocardial imaging using 111In antimyosin Fab is able to provide information to guide the course of patients receiving DOX treatment.

Animals↗

PubMed1992

Induction of endothelin-1 gene by angiotensin and vasopressin in endothelial cells.

To elucidate the cellular mechanism of endothelin-1 biosynthesis induced by angiotensin and vasopressin, we first cloned and sequenced full-length bovine preproendothelin-1 complementary DNA (cDNA) from a cultured bovine carotid artery endothelial cell cDNA library. The predicted bovine preproendothelin-1 consists of 202 amino acid residues and has a high percentage of homology to human, porcine, and rat preproendothelin-1 (70%, 81%, and 77%, respectively). Big endothelin-1, an intermediate form, consists of 39 residues differing only at position Val28 from porcine (Ile28) and His27 from rat (Arg27). The predicted 21-residue mature endothelin-1 is identical to human, porcine, rat, canine, and mouse endothelin-1. Northern blot analysis with the cloned cDNA as a probe demonstrated that a single 2.3-kb preproendothelin-1 messenger RNA (mRNA) is expressed not only in endothelial cells, but also in various bovine tissues, including lung, brain, heart, intestine, kidney, ovary, and urinary bladder. Angiotensin II and arginine vasopressin immediately and dose-dependently induced expression of preproendothelin-1 mRNA, whose effects were abolished by specific receptor antagonists. These findings suggest that stimulation of endothelin-1 secretion from endothelial cells by both agonists may be principally due to induction of preproendothelin-1 mRNA.

Amino Acid Sequence↗

PubMed1992

Endothelin-1 enhances calcium entry through T-type calcium channels in cultured neonatal rat ventricular myocytes.

Endothelin-1 (ET-1), a 21-amino acid vasoconstrictive peptide, increases intracellular Ca2+ level and has hypertrophic action on ventricular myocytes. To elucidate a possible role of Ca2+ entry through sarcolemmal Ca2+ channels on this ET-1 action, we examined effects of ET-1 on L-type (ICa,L) and T-type (ICa,T) Ca2+ currents in cultured neonatal rat ventricular myocytes using the patch-clamp technique. ET-1 at a concentration of 10 nM increased the maximum current density of ICa,T from -3.0 +/- 1.4 microA/cm2 in the control condition to -4.4 +/- 1.6 microA/cm2 (p < 0.01). Although the peak amplitude of ICa,L was decreased during ET-1 application (from -9.7 +/- 1.9 microA/cm2 in the control condition to -5.0 +/- 1.4 microA/cm2 [p < 0.01]), this magnitude of decrease in ICa,T (52 +/- 19%) was comparable to that of spontaneous "run-down" of ICa,L (47 +/- 26%). The enhancement of ICa,T by ET-1 was dose dependent; it was initiated as low as 0.32 nM, and the maximal response was attained at approximately 10 nM, with a half-maximal dose of 1.26 nM. The enhancement of ICa,T by ET-1 was antagonized by protein kinase C inhibitors staurosporine (0.2 microM) and 1-(5-isoquinolinesulfonyl)-2-methylpiperazine (H-7, 20 microM) applied to the pipette solution. Extracellular application of tumor-promoting phorbol esters, phorbol 12,13-dibutyrate (PDBu) and 4 beta-phorbol 12-myristate 13-acetate, augmented ICa,T. PDBu (0.2 microM) increased the maximal current density of ICa,T from -4.2 +/- 0.5 microA/cm2 in the control condition to -5.5 +/- 1.0 microA/cm2 (p < 0.01). In the presence of H-7 (20 microM) in the pipette solution, PDBu failed to enhance ICa,T, and an inactive isomer of PDBu (4 alpha-phorbol 12,13-dibutyrate, 0.2 microM) did not augment ICa,T. Thus, ET-1 enhances Ca2+ entry through the sarcolemmal T-type Ca2+ channel, possibly through a pathway involving activation of protein kinase C. This ET-1 action may be involved in the rise of the intracellular Ca2+ level and may contribute to the induction of cardiac hypertrophy by ET-1.

Animals↗

PubMed1992

Mineralocorticoids and acidosis regulate H+/HCO3- transport of intercalated cells.

The effects of acidosis and mineralocorticoids on cellular H+/HCO3- transport mechanisms were examined in intercalated cells of the outer stripe of outer medullary collecting duct (OMCDo) from rabbit. Intracellular pH (pHi) of intercalated cells was monitored by fluorescence ratio imaging using 2',7'-bis(carboxyethyl)-5(6)-carboxyfluorescein (BCECF). pHi recovered from an acid load at 2.8 +/- 0.5 x 10(-3) pHU/s in the absence of ambient Na+. This pHi recovery rate was similar in chronic acidosis induced by NH4Cl loading, but it was enhanced (+111%) by treatment with deoxycorticosterone acetate (DOCA). In a DOCA-treated group, luminal 10 microM SCH28080 and 0.1 mM omeprazole, H(+)-K(+)-ATPase inhibitors, did not change the pHi recovery rate, while luminal 0.5 mM N-ethylmaleimide blocked the rate by 68%. DOCA, but not acidosis, increased (approximately 40%) initial pHi response to bath HCO3- or Cl- reduction in Na(+)-free condition. After an acid load in the absence of Na+ and HCO3-, pHi response to basolateral Na+ addition was stimulated (+66%) by acidosis, but not by DOCA. Our results suggest that (a) mineralocorticoids stimulate H+/HCO3- transport mechanisms involved in transepithelial H+ secretion, i.e., a luminal NEM-sensitive H+ pump and basolateral Na(+)-independent Cl(-)-HCO3- exchange; and (b) acidosis enhances the activity of basolateral Na(+)-H+ exchange that may be responsible for pHi regulation.

Acid-Base Equilibrium↗

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↗