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Biomedical subjects

M Nakamaru

Publications and source records attributed to M Nakamaru.

At least 37 records · Page 2Linked to original sources
PubMed1990

Evidence for endothelin-1 release from resistance vessels of rats in response to hypoxia.

To elucidate further the contribution of endothelin into endothelium-dependent vasoconstriction evoked by hypoxia, we observed endothelin release during hypoxia. Endothelin was detectable in perfusate from mesenteric artery. Immunoreactive endothelin was confirmed as endothelin-1 by a reverse phase-HPLC. Endothelin release increased 4.1 +/- 1.3 to 12.4 +/- 2.0 pg/30 min without changing perfusion pressure. Thirty minutes of hypoxia stimulated endothelin release by 71 +/- 11% (P less than 0.05) and was associated with an elevation of perfusion pressure. These results suggest that endothelin contributes to endothelium-dependent vasoconstriction by hypoxia in mesenteric artery and may play an important role in the local peripheral vascular tone.

Animals↗
PubMed1990

[A case of recessive dystrophic epidermolysis bullosa associated with dwarfism with special reference to pathophysiological role of growth hormone].

Epidermolysis bullosa is a group of disorders whose common primary feature is the formation of blisters following trivial trauma. Recessive dystrophic epidermolysis bullosa (RDEB), a subtype of epidermolysis bullosa, is frequently associated with growth retardation. This growth retardation has been reported to be caused by trophopathy following protein loss through skin lesions. Endocrine disorders as the cause of growth retardation in RDEB have not been clearly described. An 11-year-old female had a typical RDEB with dwarfism. Her height was 125 cm and weight was 21 kg, both of which were 2.5 SD below the average. The skin lesions were generalized and probably caused by undernourishment, infection, and blood loss through the skin. However, her serum albumin was at the lower normal limit, and the rapid turnover proteins were slightly decreased. Endocrinological examinations revealed that all the basal levels of pituitary, thyroid, and adrenal hormones were normal. Results of the exercise test, the insulin tolerance test, and the growth hormone-releasing factor test indicated the presence of hypothalamic disorder in secretion of growth hormone. This is the first report of RDEB in which hypothalamic disorder in growth hormone secretion was investigated. On the other hand, growth hormone is known to be involved in collagen metabolism, and a decrease in collagen fibrils and an increase in collagenase activities are found in the skin of RDEB. This implies that this hypothalamic disorder in growth hormone secretion may be involved in the pathophysiology of both dwarfism and the skin lesions in RDEB.

Child↗
PubMed1990

Autoimmune neutropenia with anti-neutrophil autoantibody associated with Sjögren's syndrome.

A 74-year-old man developed neutropenia in association with Sjögren's syndrome. The peripheral neutrophils in his blood decreased to 210/mm3 (total white blood cell count 2,100/mm3). Bone marrow examination showed an increase in the number of neutrophil precursors. The presence of anti-neutrophil autoantibody (ANAB) in his plasma was determined by an enzyme-linked immunosorbent assay. Prednisolone therapy resulted in an increase in the neutrophil count and a decrease in the ANAB titer. However, when the daily dose of prednisolone was decreased, the neutrophil count gradually decreased, and the ANAB titer increased again. These results suggest that neutropenia in this patient was caused by ANAB, and ANAB could be the result of autoimmune disorders associated with Sjögren's syndrome.

Aged↗
PubMed1990

Effects of chronic converting enzyme inhibition on the vascular renin-angiotensin system.

1. The effects of chronic oral administration of inhibitors of angiotensin converting enzyme (ACE) on the vascular renin-angiotensin system were studied. 2. Male Sprague-Dawley rats were treated orally with five ACE inhibitors, captopril, enalapril, ramipril, cilazapril and CS-622 (10 mg/kg per day), for periods of 1-2 weeks. Their mesenteric arteries were then isolated and perfused in vitro with Krebs'-Ringer solution, and the angiotensin II (AII) released into the perfusate was measured under unstimulated and isoproterenol-stimulated conditions. The vascular renin activity was also determined after treatments with ACE inhibitors. 3. Treatment with captopril for 1 week suppressed the isoproterenol-stimulated increase in AII release, but had little effect on the baseline release. Oral treatment with captopril for 2 weeks or with other ACE inhibitors for 1 week markedly inhibited both the unstimulated and stimulated release of AII from the mesenteric vasculature. 4. Both the vascular renin activity and the plasma renin activity increased on captopril treatment, but their changes with time were different. 5. These results indicate that virtually complete inhibition of the vascular renin-angiotensin system can be achieved after prolonged treatment with ACE inhibitors, and suggest that the chronic antihypertensive action of ACE inhibitors is not solely due to inhibition of the plasma renin-angiotensin system.

Administration, Oral↗
PubMed1990

Effects of endothelin on neuroeffector junction in mesenteric arteries of hypertensive rats.

The effect of endothelin, a novel vasoconstrictor peptide, on the adrenergic neuroeffector junction was investigated in isolated perfused mesenteric arteries of spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats. The vasoconstrictor responses to periarterial sympathetic nerve stimulation and exogenous norepinephrine were determined. Infusion of endothelin-1 increased the baseline perfusion pressure dose dependently to similar extents in the two strains. A subpressor dose of endothelin-1 (10(-10) M) enhanced the pressor response to norepinephrine; its effect was greater in WKY rats than in SHR. Endothelin-1 (10(-12) to 10(-10) M) attenuated the pressor response to sympathetic nerve stimulation, and the degree of inhibition tended to be less in SHR than in WKY rats. Higher doses (3 x 10(-10) and 10(-9) M) of endothelin-1 enhanced the pressor response to nerve stimulation in both WKY rats and SHR. Endothelin-1 inhibited norepinephrine release from rat mesenteric arteries; the inhibition was significantly less in SHR than in WKY rats. These results suggest that endothelin enhances the responsiveness of alpha-adrenergic receptors to catecholamines, whereas it inhibits presynaptic adrenergic neurotransmission. Thus, endothelin can interact with the neuroeffector junction in addition to having a vasoconstricting effect in peripheral vessels. The difference in the mode of modulation by endothelin at the vascular neuroeffector junction in SHR from that in WKY rats might explain the maintenance of hypertension.

Animals↗
PubMed1990

[Atrioventricular delay and diastolic mitral regurgitation in patient with DDD pacemaker implantation, and cardiac function].

We examined the mitral valve motion, the mitral valve flow pattern, and changing atrioventricular (AV) delay in 34 patients with DDD pacemaker implantation, using M-mode echocardiography and pulse Doppler echocardiography. In 28 patients, B-B' step and diastolic mitral regurgitation (DMR) were induced by extending the AV delay. 8 of 12 patients who showed B-B' step and DMR with the AV delay less than or equal to 165 mS had heart failures. In such patients, P-B-B' step (DMR) interval was 174 +/- 31 mS shorter than the other patients (216 +/- 26 mS, p less than 0.001), and Q-C interval was 131 +/- 26 mS longer than the other patients (63 +/- 31 mS, p less than 0.001). The minimal value of the AV delay that induces B-B' step and DMR can be decided under the influence of cardiac functions, and this echocardiographic examination is useful, giving us information about the cardiac function of the patients with DDD-PM. B-B' step is the mitral valve motion that corresponds with the DMR, so we can check the DMR through the B-B' step easily.

Aged↗
PubMed1990

Endothelin activates the vascular renin-angiotensin system in rat mesenteric arteries.

The effects of endothelin on the vascular renin-angiotensin system were examined in isolated perfused rat mesenteric arteries by measuring vascular renin activity and angiotensin II released into the perfusate. Infusion of endothelin (10(-9)M and 10(-11)M) increased the vascular renin activity and angiotensin II release. Pretreatment with nicardipine (10(-6)M), a calcium channel blocker, significantly suppressed these effects of endothelin. These results suggest that endothelin activates the vascular renin-angiotensin system via intracellular calcium metabolism. Vascular angiotensin II produced by endothelin may modulate the local effect of endothelin on the resistance vessels.

Angiotensin II↗
PubMed1989

[Graves' disease with markedly elevated serum immunoglobulin E].

A 37-year-old female with Graves' disease was reported. An abnormally high concentration of serum IgE was observed by radioimmuno-sorbent test before treatment. Laboratory findings showed no evidence of atopic diseases or other known diseases with hyperglobulinemia E. There is no reported case of Graves' disease associated with remarkably elevated plasma IgE level. In the present patient, a further elevation of serum IgE concentration was observed when the dose of methimazole reached about 500 mg in total. Allergic mechanism may be the cause of this phenomenon. Serum IgE level was decreased gradually after replacement of methimazole by propylthiouracil. IgE level was not parallel with thyroid functions, and even when her thyroid function was normalized after subtotal thyroidectomy, IgE concentration was still increased around 900 IU/ml. The mechanism of hyperglobulinemia E in this case was discussed.

Adult↗
PubMed1989

Endothelin inhibits presynaptic adrenergic neurotransmission in rat mesenteric artery.

The effect of endothelin(ET) on adrenergic neurotransmission was examined in isolated perfused rat mesenteric arteries. Porcine ET(10(-12) to 10(-10)M) attenuated the pressor response to sympathetic nerve stimulation (NS). It also stimulated the release of prostaglandin E2 (PGE2), but its inhibition of the pressor response to NS was not affected by indomethacin treatment. ET also caused dose-dependent inhibition of [3H]norepinephrine release during NS. Higher doses of ET rather enhanced the pressor response to NS. These results suggest that ET inhibits presynaptic adrenergic neurotransmission without mediation of PGE2, while it potentiates the responsiveness of the postsynaptic alpha-adrenergic receptor. Thus ET appears to act directly on the neuroeffector junction as well as on the peripheral vasculature.

Adrenergic Fibers↗
PubMed1989

Endothelin stimulates the release of prostacyclin from rat mesenteric arteries.

The effect of endothelin on the release of prostacyclin was examined in perfused rat mesenteric arteries with or without their pretreatment with indomethacin. Porcine endothelin at 10 pmol (a subpressor dose) and 40 pmol stimulated the release of 6-keto-PGF1 alpha, a stable metabolite of prostacyclin. Rat endothelin also stimulated its release, but less than porcine endothelin. Pretreatment with indomethacin completely inhibited this 6-keto-PGF1 alpha release. These results indicate that endothelin stimulates the release of prostacyclin from mesenteric arteries. This release may modulate the action of endothelin locally.

Animals↗
PubMed1989

Endothelin enhances adrenergic vasoconstriction in perfused rat mesenteric arteries.

The interaction of endothelin with alpha-adrenergic receptors was examined in isolated perfused rat mesenteric arteries. Infusion of porcine or rat endothelin increased the baseline perfusion pressure dose-dependently. Subpressor doses of both porcine (10(-11) and 10(-10)M) and rat (10(-10) and 10(-9)M) endothelin enhanced the pressor responses to norepinephrine. Nicardipine (10(-7)M), a calcium channel blocker, attenuated this potentiation. These results suggest that endothelin enhances the responsiveness of alpha-adrenergic receptors to catecholamines probably through the increase in calcium influx. Thus endothelin may interact with sympathetic nerve activity in addition to having a direct vasoconstrictor action in peripheral vascular tissue.

Animals↗
PubMed1989

Discovery of atrial natriuretic factor in the brain: its characterization and cardiovascular implication.

1. We have devised a radioimmunoassay for atrial natriueretic factor (ANF). Its application to rat brain extract led to the discovery of ANF in the brain. In addition to the hypothalamus and the pontine medullary region, it was widely distributed. 2. ANF in the brain is stored in a low molecular weight form, in contrast to pro-ANF in the atria. Thus, the processing of pro-ANF in the bran neuronal cells is different from that in the atria. 3. ANF was found in the anterior and posterior lobes of the pituitary, the peripheral ganglia, adrenergic neurons, and the adrenal medulla. 4. Brain ANF suppressed stimulated dipsogenesis, basal and stimulated vasopressin release, and angiotensin II-stimulated pressor effects. 5. ANF in the peripheral neuronal system inhibits catecholamine synthesis and release. Thus, central ANF functions to reduce the peripheral fluid volume and vascular tone in concert with the peripheral ANF.

Animals↗
PubMed1989

Active and inactive renin in the adrenal.

Specific renin has been identified in the outer layers of the adrenals of rat, mouse, and human and the inner cortical layers but not in the medulla of mouse adrenals. Nephrectomy causes a marked elevation of adrenal renin, presumably through hyperkalemia. The subcellular distribution of adrenal renin was investigated by Percoll density gradient. The renin activity in the dense granules from the capsules of nephrectomized rats was 15 times greater than that of intact rat. Most of the active form renin was found in dense renin granules. Immunohistochemical studies revealed that the dense granules increased in number after bilateral nephrectomy. Immunogold staining of these granules showed unequivocally the presence of renin therein. Adrenal capsules in organ culture were found to release renin at a steady rate. Renin release from bilaterally nephrectomized rat adrenals was 46 times greater than from the organs of intact animals. The mechanism of the control of renin secretion from the adrenal gland was different from the kidney in that the secretion was stimulated by potassium chloride (10 mol/L) or angiotensin II (10(-9) to 10(-7) mol/L) but not by ACTH (10(-9) to 10(-7) mol/L), suggesting stimulation by intracellular calcium. These results provide evidence that the adrenal synthesizes renin, stores it in specific secretory granules, and secretes it in a regulated manner. Prorenin in the adrenal tissue accounted for only 10% of the total renin whereas 90% of the secreted renin was inactive.

Adrenal Glands↗
PubMed1989

Actions of endothelin on adrenergic neuroeffector junction.

The effect of endothelin, a novel vasoconstrictor peptide, on the adrenergic neuroeffector junction was investigated in isolated perfused rat mesenteric arteries. The vasoconstrictor responses to periarterial nerve stimulation and exogenous noradrenaline were determined. Infusion of endothelin-1 (10(-14) to 10(-8) mol/l) increased the baseline perfusion pressure dose dependently. Subpressor doses of endothelin-1 (10(-11) and 10(-10) mol/l) enhanced the pressor response to noradrenaline, and 10(-12) to 10(-10) mol/l endothelin-1 attenuated the pressor response to periarterial nerve stimulation. Endothelin-1 also caused a dose-dependent inhibition of [3H]-noradrenaline release during the periarterial nerve stimulation. However, higher doses of endothelin-1 (3 x 10(-10) to 10(-8) mol/l) enhanced the pressor response to stimulation. These results suggest that endothelin potentiates adrenergic vasoconstriction postjunctionally while it inhibits adrenergic neurotransmission. Thus endothelin may have actions on the neuroeffector junction in addition to its direct vasoconstricting effect.

Animals↗
PubMed1989

Renal interaction of atrial natriuretic peptide with angiotensin II: glomerular and tubular effects.

1. The possible interactions between the renal effects of atrial natriuretic peptide (ANP) and angiotensin II (AII) were studied in normal sodium-replete human subjects. Recent investigations have suggested that ANP inhibits the pressor and volume-retaining effects of activation of the renin-angiotensin system. Thus, ANP may attenuate the effects of AII on renal haemodynamics or tubular transport. 2. ANP (0.1 micrograms/kg per min, 60 min) was intravenously infused into eight normal human subjects with and without pretreatment with enalapril (20 mg, per oral), an inhibitor of the converting enzyme, and during infusion of AII (10 mg/kg per min). 3. ANP infusion alone caused increases in the urine volume (from 96 +/- 23 to 229 +/- 44 mL/h, P less than 0.05) and urinary sodium excretion (from 11.5 +/- 1.6 to 20.9 +/- 4.2 mEq/h, P less than 0.05). These changes were accompanied by an increase in the glomerular filtration rate (from 127 +/- 9 to 158 +/- 9 mL/min, P less than 0.05). ANP infusion after enalapril administration lowered the mean blood pressure (from 76 +/- 2 to 71 +/- 3 mmHg, P less than 0.05) to a level similar to that observed during ANP infusion alone (from 84 +/- 2 to 74 +/- 2 mmHg, P less than 0.01), but did not result in a significant diuresis (from 139 +/- 23 to 174 +/- 51 mL/h) or natriuresis (from 19.7 +/- 2.5 to 14.3 +/- 3.4 mEq/h, P less than 0.05). This combined treatment with a converting enzyme inhibitor and ANP reduced both the glomerular filtration rate (160 +/- 9 to 141 +/- 10 mL/min) and the renal plasma flow (from 775 +/- 49 to 570 +/- 45 mL/min, P less than 0.01). 4. The antinatriuretic effects of exogenous AII were reversed by superimposed ANP infusion (urinary sodium excretion: from 4.8 +/- 1.0 to 24.3 +/- 5.2 mEq/h, P less than 0.01). Under these conditions, the glomerular filtration rate increased (from 114 +/- 6 to 156 +/- 7 mL/min, P less than 0.05) to levels similar to those observed with ANP infusion alone. In addition the increased tubular sodium reabsorption induced by AII was inhibited by concomitant ANP infusion (fractional proximal tubular sodium reabsorption: from 90.7 +/- 3.5 to 80.3 +/- 16.6%, P less than 0.05, fractional post-proximal tubular sodium reabsorption: from 91.5 +/- 9.8 to 87.6 +/- 8.8%, P less than 0.05).(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1989

Renin inhibitor and converting enzyme inhibitors suppress vascular angiotensin II.

The direct effects of a renin inhibitor, N-acetyl-pepstatin and five angiotensin converting enzyme inhibitors, captopril and the active diacid forms of enalapril, ramipril, cilazapril, and CS-622, on the vascular renin-angiotensin system were examined in isolated perfused rat mesenteric arteries. Vascular renin activity and angiotensin II (Ang II) released into the perfusate were determined. Infusion of N-acetyl-pepstatin (5 X 10(-8)-5 X 10(-6) M) suppressed vascular renin activity and Ang II release dose dependently. Isoproterenol (10(-6) M) induced a 135 +/- 30% increase in Ang II release from the basal value. N-Acetyl-pepstatin (5 X 10(-6) M) suppressed isoproterenol-induced Ang II release. Infusions of 5 X 10(-6) M captopril and the diacid forms of enalapril, ramipril, cilazapril, and CS-622 by themselves had little effect on Ang II release, but concomitant infusion of isoproterenol with these angiotensin converting enzyme inhibitors significantly decreased Ang II release (71 +/- 21%, 51 +/- 40%, 8 +/- 21%, 69 +/- 24%, and 44 +/- 29% increase, respectively, from the basal values). These results indicate that N-acetyl-pepstatin suppresses the vascular renin-angiotensin system. This effect may in part contribute to the hypotensive actions of renin inhibitors. Although angiotensin converting enzyme inhibitors also suppress locally generated Ang II, the mechanism and physiological significance still remain to be clarified.

Angiotensin II↗
PubMed1989

Effect of atrial natriuretic peptide on catecholamine release from human pheochromocytoma.

The effect of synthetic alpha human atrial natriuretic peptide on catecholamine release from human pheochromocytomas was studied both in vivo and in vitro. Iv infusion of atrial natriuretic peptide at a rate of 0.1 microgram.kg-1.min-1 for 60 min into two normotensive patients with pheochromocytoma caused a small decrease in the mean blood pressure, increase in the heart rate, and marked increase in the plasma level of norepinephrine (2.08 to 6.83 nmol/l, and 1.15 to 2.83 nmol/l, respectively) compared with 0.60 +/- 0.10 to 1.19 +/- 0.20 nmol/l in normal subjects. Treatment with atrial natriuretic peptide also increased the plasma epinephrine level from 0.34 to 1.27 nmol/l, and from 0.67 to 0.79 nmol/l in the patients with pheochromocytoma, but not in the normal subjects (0.05 +/- 0.01 to 0.05 +/- 0.01 nmol/l). After removal of the tumour, the responses of the plasma norepinephrine and epinephrine to atrial natriuretic peptide infusion were normalized. There was no significant effect of 10(-8) to 10(-5) mol/l atrial natriuretic peptide on the basal release of catecholamines from isolated superfused pheochromocytoma tissue. Atrial natriuretic peptide (10(-7) mol/l) did not affect the increase in catecholamine release induced by glucagon (10(-5) mol/l). These results suggest that the exaggerated responses of plasma catecholamines to atrial natriuretic peptide in patients with pheochromocytoma may be due to a washout effect resulting from change in blood flow in the vessels feeding the tumour rather than increased sympathetic nerve activity induced by hypotension and hypovolemia. The results also suggest that atrial natriuretic peptide dose not have any direct action on pheochromocytoma tissue causing catecholamine release.

Adrenal Gland Neoplasms↗