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M Kageyama

Publications and source records attributed to M Kageyama.

At least 73 records · Page 4Linked to original sources
PubMed1991

Antihypertensive effect of a novel calcium antagonist, SD-3211, in experimental hypertensive rats.

The antihypertensive effect of SD-3211, a structurally novel type of nondihydropyridine calcium antagonist, was assessed using several types of experimental hypertensive rats. Oral administration of SD-3211 (10, 20, and 30 mg/kg) to conscious spontaneously hypertensive rats (SHR), deoxycorticosterone acetate-salt hypertensive rats (DHR) and 2-kidney, 1-clip renal hypertensive rats (RHR) resulted in a dose-dependent decrease in systolic blood pressure (SBP). The hypotensive effect of SD-3211 in these hypertensive rats was more pronounced than in normotensive rats (NR). The potencies of SD-3211 for the hypotensive effect in the hypertensive rats and NR were 5-7 times greater than that of diltiazem but 2-3 times less than that of nicardipine. Furthermore, SD-3211 showed longer-lasting hypotensive action than diltiazem and nicardipine, at the respective equihypotensive dose. During the course of hypotension, SD-3211 did not exert any influence on heart rate (HR) in any type of hypertensive rats or NR, in contrast to the appearance of tachycardia with nicardipine in SHR, DHR, and NR and of bradycardia with diltiazem in DHR. At doses of 10 and 30 mg/kg, the hypotensive doses, SD-3211 elicited a dose-dependent natriuresis but no kaliuresis in SHR. In the chronic study using SHR, SD-3211 at 10 mg/kg/day showed an antihypertensive effect during an administration period of 12 consecutive weeks. These results allow us to conclude that SD-3211 has a potent and long-lasting hypotensive action with little cardiac effect.

Animals↗
PubMed1991

Is staurosporine a specific inhibitor of protein kinase C in intact porcine coronary arteries?

We assessed the specificity of staurosporine, a putative protein kinase C inhibitor, for the enzyme in intact porcine coronary arteries by examining its effects on changes in intracellular free calcium level ([Ca++]i) and force induced by a phorbol ester, high KCl and caffeine. [Ca++]i was measured simultaneously with force by the fura-2 microfluorimetric method. Phorbol 12,13-dibutyrate (PDBu, 10(-6) M) produced a slowly developing and sustained contraction; however, [Ca++]i only increased slightly and transiently in the initial phase and then decreased gradually. On the other hand, 90 mM KCl elicited a contraction with a sustained increase in [Ca++]i. Staurosporine (10(-10) to 10(-7) M) applied 20 min before the addition of PDBu inhibited the PDBu-induced changes in [Ca++]i and force in a concentration-dependent manner. In contrast, staurosporine only at 10(-7) M reduced an increase in [Ca++]i and contractile force produced by 90 mM KCl. The inhibitory effects of staurosporine on PDBu- and KCl-induced contractions depended on exposure time. The [Ca++]i-force relationship obtained with variable concentrations of KCl was shifted slightly to the right by staurosporine at 10(-7) M. Furthermore, staurosporine even at 10(-7) M did not affect an increase in [Ca++]i by caffeine (25 mM), although it slightly attenuated a caffeine-induced contraction. These results suggest that staurosporine is a relatively specific inhibitor of protein kinase C in intact arteries at lower concentrations. At higher concentrations it may have actions unrelated to its inhibitory effect of protein kinase C, which include the inhibition of calcium influx into smooth muscle cells through the voltage-dependent Ca++ channel.

Alkaloids↗
PubMed1990

Inhibitory effects of nisoldipine and saralasin on angiotensin II-induced antidiuresis in anesthetized dogs.

Inhibitory effects of the calcium channel blocker nisoldipine on angiotensin II-induced antidiuresis were investigated in anesthetized dogs, and the findings were compared with those of saralasin. Intrarenal arterial infusion of 10 ng/kg/min angiotensin II resulted in marked decreases in renal blood flow (RBF) and urine formation, with a relatively moderate decrease in glomerular filtration rate. There were marked reductions in the fractional excretion of lithium, which is used as an index of the fractional proximal excretion of sodium, and the fractional distal excretion of sodium. Nisoldipine (50 ng/kg/min) administered intrarenally produced a partial inhibition on the decreased response of RBF to angiotensin II. The peptide-induced decreases in urine flow, urinary excretion of electrolytes and fractional excretion of electrolytes were abolished by nisoldipine. In contrast, when saralasin was administered intrarenally at 10 ng/kg/min, a dose which could partially inhibit the angiotensin II-induced decrease in RBF to the same extent as seen with nisoldipine, the antagonist attenuated, but did not abolish, the antidiuretic action of angiotensin II. Significant decreases in urine formation by angiotensin II were observed, even in the presence of saralasin. These results suggest that nisoldipine, unlike saralasin, preferentially interferes with the stimulatory effect of angiotensin II, as related to the renal tubular reabsorption of sodium and water.

Anesthesia↗
PubMed1989

Inhibitory effect of nisoldipine on angiotensin-II-induced renal actions in anesthetized dogs.

Renal effects of nisoldipine, a potent calcium channel blocker, were examined in anesthetized dogs. Intrarenal arterial infusion of nisoldipine (2, 10, and 50 ng/kg per min) had no effect on mean systemic blood pressure and heart rate and there was no significant change in renal hemodynamics during infusion of various doses of the drug. Urine flow and urinary excretions of sodium, chloride, and potassium were increased by nisoldipine in a dose-related manner. Fractional excretions of sodium and chloride were markedly elevated with the highest dose given thereby indicating that tubular reabsorptions of sodium and chloride were inhibited by nisoldipine. Nisoldipine (50 ng/kg per min) abolished the decreasing effects of angiotensin-II on glomerular filtration rate, urine flow, and urinary excretion of electrolytes but not the decrease in renal blood flow by the peptide. Angiotensin-II-induced reduction of fractional excretion of electrolytes was completely blocked by nisoldipine. Renal responses to norepinephrine were unaffected by nisoldipine. Thus, nisoldipine administered intrarenally to anesthetized dogs exerts a diuretic action by way of tubular effects, as is the case with other dihydropyridine calcium channel blockers. Nisoldipine seems to effectively antagonize the renal response to angiotensin-II. Thus, the preferential inhibition of angiotensin-II-induced antidiuresis may mean that nisoldipine interferes with stimulatory effects of angiotensin-II on the renal tubular reabsorption of electrolytes and water.

Anesthesia↗
PubMed1989

Diuretic effect induced by intrarenal infusion of nisoldipine in anaesthetized dogs.

1. Renal effects of nisoldipine, a potent calcium channel blocker, were examined in anaesthetized dogs. 2. Intrarenal arterial infusion of nisoldipine (10, 50 ng/kg per min) did not influence mean systemic blood pressure and renal haemodynamics, but did cause dose-related increases in urine flow and urinary excretion of electrolytes. During nisoldipine infusion at the higher dose, the levels of fractional excretion of sodium, potassium and chloride were significantly elevated. 3. In the lithium clearance study, fractional lithium excretion, an index of fractional sodium excretion in the proximal tubules, was unchanged even with the higher dose of nisoldipine, whereas fractional sodium excretion in the distal tubules markedly increased. 4. Nisoldipine elicited a significant increment in osmolar clearance without altering the reabsorption of free water. 5. Thus, intrarenal administration of nisoldipine at a non-hypotensive dose to anaesthetized dogs produced a significant diuretic effect without alteration in renal haemodynamics. Results in lithium clearance and free water clearance studies suggest that nisoldipine exerts a diuretic action by inhibiting sodium transport at the distal nephron segments beyond the proximal tubules.

Anesthesia↗
PubMed1988

Stimulatory effects of neuronally released norepinephrine on renin release from rat kidney cortical slices.

Stimulatory effects of extracellular high K+ in the presence of nifedipine (NIF) on renin release (RR) from kidney cortical slices were investigated. The stimulation was suppressed either by propranolol or by metoprolol but not by prazosin. High K+ plus NIF-induced increase in RR was attenuated by renal denervation. The enhancing effect was not observed when the slices were incubated in Ca2+-free buffer or in medium containing divalent cations such as Cd2+, Co2+ and Mn2+. These alterations in RR correlated with 3H-efflux from the slices preloaded with 3H-norepinephrine. We conclude that the high K+ plus NIF-induced increase in RR from the slices is mediated by norepinephrine (NE) derived from renal sympathetic nerves and that this neuronally released NE stimulates RR via the activation of beta-adrenoceptors.

Animals↗
PubMed1988

Stimulatory effects of neuronally released norepinephrine on renin release in vitro.

Extracellular high potassium inhibits renin release in vitro by increasing calcium concentrations in the juxtaglomerular cells. We found that the decreased response of renin release from rat kidney cortical slices in high potassium solution (20-80 mM) changed to a strikingly increased one in the presence of nifedipine at doses over 10(-6) M. We then examined the stimulatory effect of extracellular high potassium in the presence of nifedipine on renin release. The enhancement of release was significantly suppressed either by propranolol or by metoprolol but not by prazosin. High potassium plus nifedipine-induced increase in renin release was markedly attenuated by renal denervation. The enhancing effect was not observed when the slices were incubated in calcium-free medium. Divalent cations such as Cd2+, Co2+, and Mn2+ (0.1-3.0 mM) blocked this enhancement in a concentration-dependent manner. High potassium elicited an increase in 3H efflux from the slices preloaded with [3H]norepinephrine. The increasing effect was not influenced by nifedipine but was abolished by the removal of extracellular calcium or by the addition of divalent cations. These observations suggest to us that the high potassium plus nifedipine-induced increase in renin release from the slices is mediated by norepinephrine derived from renal sympathetic nerves and that this neuronally released norepinephrine stimulates renin release via activation of beta-adrenoceptors.

Animals↗
PubMed1987

The sequence and function of the recA gene and its protein in Pseudomonas aeruginosa PAO.

The recA gene of Pseudomonas aeruginosa has been isolated and its nucleotide sequence has been determined. The coding region of the recA gene has 1038 bp specifying 346 amino acids. The recA protein of P. aeruginosa showed a striking homology with that of Escherichia coli except for the carboxy-terminal region both at the nucleotide and amino acid level. The recA+-carrying plasmids restored the UV sensitivity and recombination ability of several rec mutants of P. aeruginosa. The precise location of the recA gene on the chromosome was deduced from the analysis of R' plasmids.

Amino Acid Sequence↗
PubMed1987

Diuretic effect induced by intrarenal infusion of pinacidil in anesthetized dogs.

The diuretic action of pinacidil, a new vasodilating antihypertensive agent, was studied using anesthetized dogs. Intrarenally administered pinacidil (0.4, 2.0 and 10 micrograms/kg/min) produced a dose-related increase of renal blood flow, without altering mean arterial pressure. The glomerular filtration rate significantly increased only with the highest dosage. Pinacidil caused a dose-related augmentation of urine formation and, when given at 10 micrograms/kg/min, increased urine flow and urinary excretion of electrolytes to about 10 times and 3 to 9 times over the respective control value. In comparison, hydralazine (4.0 and 20 micrograms/kg/min) produced no significant diuretic action and bradykinin, given at a dose (0.02 micrograms/kg/min) equipotent to pinacidil (10 micrograms/kg/min) with respect to increasing renal blood flow, was less effective. Pinacidil administration significantly increased the fractional excretion of phosphate. Thus, pinacidil-induced diuresis seems to be due mainly to the vasodilating effect on renal vessels, with some contribution from an inhibitory effect on sodium reabsorption in the proximal tubules.

Anesthesia↗
PubMed1986

The different effects of exogenous and neuronally released norepinephrine on renin release in rat kidney cortical slices.

The effects of veratrine on renin release from rat kidney cortical slices were compared with those of norepinephrine (NE). Veratrine (10-100 micrograms/ml) produced a concentration-dependent increase in renin release. This action was markedly attenuated by propranolol but not influenced by prazosin. On the other hand, relatively higher concentrations of NE produced an inhibition of renin release and the inhibitory action was reversed by prazosin. These results suggest that exogenous NE inhibits renin release by preferential activation of alpha 1-adrenoceptors while neuronally released NE stimulates renin release by exclusive activation of beta-adrenoceptors.

Animals↗
PubMed1985

Ultrastructural visualization of elastic fibres with a tannate--metal salt method.

A modification of the tannic acid-metal salt method was applied as an ultrastructural stain for elastin. Thin sections of glutaraldehyde-fixed, embedded rat aorta and rabbit elastic cartilage, with and without osmication, were examined. Raising the pH of the tannic acid solution from 2.7 to 9.0 progressively increased the electron-density of elastic fibres and collagen fibrils in osmicated and unosmicated specimens. The maximum tannic acid staining of elastic fibres was observed in the pH range 7.0-9.0. Collagen staining, although less intense than that of elastic fibres, was also greatest in this pH range. Elastic fibres in osmicated specimens demonstrated the strongest tannic acid staining with a minimal increase in density of collagen and cell nuclei when compared to the unosmicated specimens. Sequential treatments of osmicated specimens with tannic acid pH 7.0-9.0, and uranyl acetate, pH 4.1, enhanced the density of the elastin intensely, increased collagen staining moderately, but hardly increased the density of nuclei and microfibrils. In elastase-digested osmicated specimens, all tannic acid (pH 7.0)-uranyl acetate-reactive elastin was selectively removed. These results demonstrate that all the neutral and alkaline tannic acid-uranyl acetate methods can be used as a postembedment stain for elastin specimens fixed in glutaraldehyde and osmium tetroxide.

Animals↗
PubMed1984

Genetic determinant of pyocin AP41 as an insert in the Pseudomonas aeruginosa chromosome.

The genetic determinant for pyocin AP41 , a bacteriocin produced by Pseudomonas aeruginosa PAF, was transferred to P. aeruginosa PAO and analyzed. By conjugation experiments, the pyocin determinant was found to be located on the chromosome, being closely linked to argG at about 45 min on the genetic map. Cloning of the pyocin AP41 gene into the plasmid R68.45 was attempted in vivo by taking advantage of its linkage at argG. R' argG+ plasmids were isolated by interspecific conjugation between P. aeruginosa and Escherichia coli recA argG strains. Some of the R' argG+ plasmids did contain the pyocin AP41 determinant. Genetic and physical analyses of these R' plasmids indicated that the pyocin AP41 determinant was located within a 2.9-kilobase extra segment found at a certain position of the chromosome of various pyocin AP41 producer strains.

Bacteriocins↗
PubMed1983

Ultrastructural distribution of sulfated complex carbohydrates in elastic cartilage of the young rabbit.

Sulfated glycosaminoglycans are an integral component of elastic cartilage. We have investigated the ultrastructural distribution of sulfated complex carbohydrates (CC) in the mature cartilage and the perichondrium of young rabbit auricles using the high iron diamine-thiocarbohydrazide-silver proteinate (HID-TCH-SP) and the tannic acid-ferric chloride (TA-Fe) methods. In the mature cartilage, HID-TCH-SP stained intracellular Golgi saccules of the mature face, secretory granules, and the extracellular matrix granules, but staining was not discernible in collagen fibrils and osmiophilic elastic fibers consisting of only amorphous elastin. The HID and TA-Fe staining were similarly observed in matrix granules, whereas the elastic fibers and collagen fibrils lacked the staining. The pericellular matrix granules had a diameter of 34 +/- 5 nm (mean +/- SD; n = 30). Thiéry's periodate-TCH-SP (PA-TCH-SP) method stained vicinal glycol-containing CC in collagen fibrils but failed to stain matrix granules and elastic fibers. In the perichondrium, HID-TCH-SP staining of the organelles was less intense in the flattened chondrocytes when compared with those in large mature chondrocytes. The extracellular HID and HID-TCH-SP staining were observed in the matrix granules. The diameter of pericellular matrix granules (19 +/- 4 nm, mean +/- SD; n = 30) was significantly smaller when compared to those in the mature cartilage (P less than 0.001). The HID-TCH-SP staining was closely associated with collagen fibrils. However, the staining was not seen in collagen fibrils and osmiophilic elastic fibers consisting of elastin and microfibrils. The PA-TCH-SP method stained collagen fibrils and microfibrils but did not stain the amorphous elastin. Thus these studies demonstrate that sulfated CC are packaged in chondrocyte secretory granules and are released into the extracellular matrix to form matrix granules, but are not incorporated into collagen fibrils and elastic fibers.

Animals↗