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H Sokabe

Publications and source records attributed to H Sokabe.

At least 37 records · Page 2Linked to original sources
PubMed1984

Pharmacodynamic and pharmacokinetic studies on prizidilol and nipradilol (K-351), antihypertensive drugs with combined vasodilator and beta-adrenoceptor blocking actions, in rabbits.

Effects of prizidilol and nipradilol (K-351), beta-adrenoceptor antagonists with vasodilator action, on blood pressure and heart rate were studied in normotensive conscious rabbits after i.v. administration. In addition, we investigated relationships between plasma drug concentrations and beta-adrenoceptor blocking activity as estimated by the inhibition of isoproterenol-induced tachycardia and vasodilator activity as assessed by the inhibition of pressor response to angiotensin II (ANG II). Prizidilol (4 mg/kg) produced a significant and sustained fall in blood pressure and a slight increase in heart rate, while hydralazine (2 mg/kg) caused the same degree of hypotension and a marked tachycardia. Nipradilol (1 mg/kg) caused a significant reduction of resting heart rate, but had no significant effect on blood pressure. Propranolol (1 mg/kg) did not affect resting blood pressure and heart rate. Hypertensive response to ANG II was significantly attenuated only by hydralazine. Isoproterenol-induced tachycardia was significantly suppressed by prizidilol, nipradilol and propranolol. Good correlations were observed between beta-adrenoceptor blocking activity and plasma drug concentrations. These data suggest that prizidilol has an advantage over hydralazine to induce less tachycardia, but still may cause a certain degree of increase in heart rate. Nipradilol has a more potent beta-adrenoceptor blocking action than propranolol, while its vasodilator action is not obvious, at least in rabbits. Plasma concentrations of prizidilol and nipradilol are good indicators for beta-adrenoceptor blocking activity, but not for vasodilator activity.

Adrenergic beta-Antagonists↗
PubMed1983

Behavior of fluorescent granular perithelium (FGP) in cerebral cortex of SHR-SP rats under some conditions.

The fluorescent granular perithelial cells (FGP) in control and experimental specimens of SHR-SP rats were studied with light and electron microscopes. The results obtained are as follows. The FGP in SHR-SP rats are localized along small cerebral vessels and provided with many irregularly shaped inclusion bodies. Their matrices are homogenous and relatively less dense. Sometimes, the FGP fall into degeneration and their cytoplasm shrinks and fills with small dense granules. Concomitantly, collagen fibers appear surrounding them. After feeding rats a fat-rich chow, lipoidal substances appear in intracellular granules of FGP at the light microscopical level. Electron microscopically, the FGP are swollen and their inclusion bodies vary in shape and content. Large inclusion bodies are composed of several middle-sized inclusion bodies with heterogenous matrices. Frequently, pale inclusion bodies are provided with intensely stained limiting membranes. These facts suggest an incorporation of fat into the FGP. With the administration of elastase, intracellular lipid decreases moderately and the FGP scarcely swell. The cytoplasm of FGP and the contents of inclusion bodies become defined and contrasty. From this evidence, elastase seems to facilitate a fat metabolism in FGP. Morphological and functional differences between FGP and other perivascular cells including pericytes, microglia, and mast cells are briefly discussed.

Animals↗
PubMed1983

Chemical structures of angiotensins formed by incubating plasma with the kidney and the corpuscles of Stannius in the chum salmon, Oncorhynchus keta.

The chemical structures of salmon angiotensins produced by incubating tissue extract of the kidney or the corpuscles of Stannius (CS) with homologous plasma are proposed. Two angiotensins, [Asp1, Val5, Asn9] and [Asn1, Val5, Asn9] angiotensin I, were proposed from both kidney and CS incubations by amino acid analysis and the fluorescent peptide-mapping techniques. CS angiotensins were not organ specific, because these two angiotensins were produced by both kidney and CS incubations in a ratio of 1:2 under the same conditions. Whether [Asp1, Val5, Asn9] angiotensin I is a naturally occurring form remains to be clarified; however, [Asn1, Val5, Asn9] angiotensin I may be the major form of angiotensin formed from plasma by salmon kidney and CS.

Amino Acid Sequence↗
PubMed1983

Chemical structure of angiotensin in the bullfrog Rana catesbeiana.

Crude bullfrog angiotensin was prepared by modified Boucher's procedures. The kidney extract was incubated in vitro with homologous plasma. Crude angiotension, 15 micrograms equivalent to [Asp1, Ile5]angiotensin II in rat vasopressor assay, was purified further by three steps by SEP-PAK C18 cartridge, SP-Sephadex column chromatography, and high-performance liquid chromatography on Finepak SIL C18 column. Amino acid analysis was done on 64 ng of the purified material after acid hydrolysis. The fluorescent peptide mapping technique was used to confirm the amino acid sequence. It is proposed that bullfrog angiotensin is [Asp1, Val5, Asn9]angiotensin I.

Amino Acid Sequence↗
PubMed1983

Effects of acute and chronic treatments with atenolol and propranolol on cardiovascular responses to handling stress in spontaneously hypertensive rats.

Although the mechanism of antihypertensive action of beta-adrenergic blocking drugs (beta-blockers) is not known, a theoretical advantage of cardioselective beta-blockers over nonselective ones has been proposed in the treatment of hypertension. To study this hypothesis, we examined cardiovascular responses to handling stress in spontaneously hypertensive (SHR) rats after a single (100 mg/kg) and multiple oral treatments (100 mg/kg per day for 17 d) with either atenolol or propranolol. Atenolol and propranolol markedly suppressed the tachycardia induced by handling stress after acute and chronic administration. Resting mean arterial pressure (MAP) was reduced by acute and chronic atenolol treatment, but not by propranolol. Stress-induced increase in MAP was significantly reduced by chronic treatment with propranolol, whereas no consistent effects were observed with atenolol. Acute treatment with guanethidine (30 mg/kg) markedly reduced the rise in MAP induced by stress. These results suggest that suppression of cardiac function by beta-blockers does not always attenuate the rise in MAP induced by stress, thus cardioselective beta-blockers might not confer any further reduction of the blood pressure increase due to sympatho-adrenal excitation. Inhibition of stress-induced MAP rise by propranolol could be mediated by a modulation of the catecholamine release.

Adrenergic beta-Antagonists↗
PubMed1982

The ratio of cardiac to vascular beta-receptor blockade of atenolol and propranolol in spontaneously hypertensive rats in vivo.

Ratios of cardiac to vascular beta-receptor blockade (C:V ratios) of atenolol and propranolol were determined in pentobarbital anesthetized spontaneously hypertensive (SHR) rats. These values and the cardiovascular responses to isoproterenol were compared with those of age-matched normotensive control (Donryu, DON) rats reported previously. Mean blood pressure (BP) and heart rate (HR) were recorded. Full dose-response curves for isoproterenol were constructed in BP and HR. In vivo pD2 values of isoproterenol (potencies), were not different between DON and SHR rats, although the maximal responses to isoproterenol (efficacy) were significantly suppressed in SHR rats. C:V ratios of atenolol and propranolol in SHR rats were 7.95 and 0.44, respectively. As the values in DON rats were 9.77 and 1.20, respectively, C:V ratios of atenolol and propranolol were decreased in SHR rats. Markedly decreased C:V ratios of propranolol in SHR rats may explain its relatively weak antihypertensive action.

Animals↗
PubMed1982

Plasma renin activity determined by two different methods in spontaneously hypertensive rats.

As a discrepancy exists between two reports from our laboratory on plasma renin activity (PRA) in spontaneously hypertensive rats (SHR), we undertook to examine the reasons for this discrepancy. PRA in SHR at 15 weeks of age was determined by two different methods, utilizing the procedures of Boucher et al or of Haber et al. For normotensive controls, Donryu (DON) and Wistar-Kyoto (WKY) rats were used. By Boucher's method, PRA in SHR was significantly lower than in DON, but did not differ from WKY. By Haber's method, PRA in SHR did not significantly differ from DON or WKY. However, the value in DON was significantly higher than in WKY. The present study basically confirmed our previous results, concluding that PRA in SHR at 15 weeks of age is within the normal range. A previous suggestion that PRA in SHR is suppressed as a result of blood pressure elevation must be revised, because it was derived from results considering only the DON strain as the control.

Angiotensinogen↗
PubMed1981

A simple method to determine the ratio of cardiac to vascular beta-receptor blockade in the rat in vivo.

We have devised a simple method to determine the ratios of cardiac to vascular beta-receptor blockage (C:V ratios) in normotensive rats anesthetized with pentobarbital, and applied it to six beta-adrenergic blocking drugs (beta-blockers). Mean blood pressure (BP) and heart rate (HR) were recorded. Isoproterenol (3 ng-100 microgram/kg, i.v.) was cumulatively injected before and after the intravenous administration of beta-blockers at two dose-levels. Thus shifts of the dose-response curves in BP and HR were observed. "In vivo pA2" values were calculated in molar doses per kg by Schild plots. The C:V ratio was calculated as antilogarithm of the difference of the mean in vivo pA2 value in HR from that in BP. Those of atenolol, bometolol, bunitrolol, pindolol, propranolol, and sotalol were 9.77, 8.13, 2.95, 1.38, 1.20, and 0.71, respectively.

Adrenergic beta-Antagonists↗
PubMed1981

Acute and subchronic effects of bometolol on blood pressure in hypertensive rats.

Bometolol is a cardiospecific beta-adrenergic blocking drug. The effect on blood pressure was determined in hypertensive rats in acute and subchronic experiments. In acute experiment bometolol, 10-30 mg/kg, p.o., was given to spontaneously hypertensive rats; deoxycorticosterone and salt hypertensive rats; and two kidney, one clip hypertensive rats. Blood pressure was determined continuously for 8 h and after 24 h in unanesthetized condition. The blood pressure lowered by bometolol was dose-dependent in three types of hypertension. In subchronic experiment, bometolol at a dose of 10-30 mg/kg or 100-300 mg/kg, p.o., were given for 5 weeks to deoxycorticosterone and salt hypertensive rats; and two kidney, one clip hypertensive rats. Bometolol did not show antihypertensive effect in either type of hypertension, although bometolol decreased heart rate dose-dependently. Bometolol treatment at the above doses decreased plasma renin activity, heart and kidney weights, and incidence of vascular lesion in either hypertensive rat. Toxic symptom was seen 3 days after bometolol treatment of 300 mg/kg in deoxycorticosterone and salt hypertensive rats.

Adrenergic beta-Antagonists↗
PubMed1981

Action of fragments of human parathyroid hormone on blood pressure in rats.

To investigate localization of the action on blood pressure in the peptide chain of parathyroid hormone (PTH), we determined the effect of seven fragments of human (h) PTH-(1-34) fragments on blood pressure in anesthetized rats. hPTH-(1-7) and -(28-34) fragments had no effect up to 1 X 10(-6) mole/kg. hPTH-(8-34), -(13-34), -(18-34), and -(23-34) fragments showed significant hypotensive activity. The decrease in the chain length lowered the hypotensive activity. The results indicate that some amino acids in position 23-34 are necessary for the hypotensive activity. This accords with the previous report suggesting that 5 amino acids in position 24-28 are essential. In addition hPTH-(8-34) and -(13-34) fragments showed initial transient hypertensive activities. hPTH-(1-13) fragment had only hypertensive action, suggesting that some amino acids in position 8-13 are necessary for hypertensive activity.

Animals↗
PubMed1980

Effects of beta-adrenergic blocking drugs in hypertensive rats.

Antihypertensive effects of three beta-adrenergic blocking drugs, acebutolol, propranolol, and practolol were studied for 11 weeks. Spontaneously (SHR); one-clip, two-kidney (CLIP); and deoxycorticosterone and salt (DOC) hypertensive rats were used. The drugs were given orally, 100 mg/kg per day, 5 days per week before development of hypertension. Propranolol inhibited blood pressure (BP) increase significantly in SHR. Acebutolol and practolol also lowered BP in SHR. Three drugs did not affect BP in CLIP, but an apparent inhibition was seen when the results were analyzed including the cases of which BP stayed below 150 mmHg. Either of three drugs did not show antihypertensive effects in DOC. Acebutolol rather increased BP more rapidly. Practolol also increased BP slightly more rapidly. Cerebral stroke was seen in DOC. The incidences of the stroke in the groups given the solvent, acebutolol, propranolol, and practolol were 3/6, 4/7, 2/6, and 3/6, respectively. Acebutolol seemed to cause stroke earlier with the more rapid BP elevation. Acebutolol, propranolol, and practolol decreased incidence of the vascular disease in CLIP. Propranolol also decreased it in DOC. Plasma renin activity was suppressed by these drugs in SHR and CLIP. The mechanisms of antihypertensive effects of beta-adrenergic blocking drugs are unknown. The present study denies those due to inhibition of cardiac function, or renin release from the kidney. A better experimental model is necessary to study this. The possibility that acebutolol and other beta-blockers might accelerate BP elevation and incidence of stroke must be reexamined.

Acebutolol↗