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Biomedical subjects

H Sokabe

Publications and source records attributed to H Sokabe.

At least 55 records · Page 3Linked to original sources
PubMed1980

Combined effects of phenoxybenzamine and propranolol in hypertensive rats.

A hypothesis that the beta-adrenergic blocking drugs may possess weak alpha-adrenergic blocking activity, and that their antihypertensive effect may be due to this combined alpha - and beta-adrenergic blockade was tested. Phenoxybenzamine (PBZ) and propranolol (PPL) were selected as alpha - and beta-blocking drugs, respectively. They were given orally at doses of 1--100 mg/kg per day, 5 days per week. Their combined antihypertensive effects were determined in spontaneously hypertensive; deoxycorticosterone and salt hypertensive; and two kidney, one clip renal hypertensive rats. PBZ treatment showed antihypertensive effect in three models of hypertensive rats. However, addition of PPL either did not affect or rather antagonized the effect of PBZ. Moreover, the combined treatment increased side-effects, typically seen as urinary incontinence. The results did not support the above hypothesis, at least when the blockade was caused with PBZ and PPL.

Animals↗
PubMed1980

Effects of long-term treatments with captopril on blood pressure and renin activity in the stroke-prone spontaneously hypertensive rats.

Antihypertensive effects of captopril, an orally active converting enzyme inhibitor were examined in the young and adult stroke-prone SHR (SHRSP) rats. The treatment was initiated at 6-7 and 14-18 weeks of age, and was continued for 12 and 17 weeks, respectively. The dosage of captopril was changed stepwise 3-30 and 3-100 mg/kg, orally per day in the young and adult rats, respectively. The effects of hydralazine were also determined for comparison. Captopril had a chronic antihypertensive effect when given in doses of 30 mg/kg in the young and 100 mg/kg in the adult rats. Captopril had no significant effect on heart rate throughout the experiments, while hydralazine increased the heart rate. Treatment with captopril decreased the incidence of vascular disease in the young and the severity in the adult rats, respectively. A decrease in incidence of cerebral stroke in the adult SHRSP was also apparent. More than a ten fold increase in plasma renin activity and about a two fold increase in kidney renin activity were observed in both the young and adult SHRSP at the end of the treatments. The results demonstrate the efficacy of long-term treatment with captopril in the management of hypertensive disease in SHRSP rats.

Animals↗
PubMed1980

Variation of plasma and kidney renin activities among substrains of spontaneously hypertensive rats.

Plasma and kidney renin activity (PRA, KRA) were determined in the spontaneously hypertensive (SHR) rats, the stroke-resistant and -prone substrains (SHRSR, SHRSP) from 5 to 30 weeks of age. Results were compared with those of two normotensive strains, Wistar-Kyoto (WKY) and Donryu (DON) rats. PRA in the SHRSP at 20 and 30 weeks of age were significantly increased when compared to other strains of rats (P < 0.01). In SHRSP rats at these ages, blood pressure exceeded the critical level of 220 mmHg and cerebral lesions were observed in 41% at autopsy. There were no significant differences in PRA among other hypertensive and normotensive strains. KRA in three substrains of the SHR were normal or subnormal as compared to WKY and DON rats. These results indicate that a direct role of the renin-angiotensin system in the SHR and its substrains can be excluded in the initiation and the maintenance of hypertension. However, the activated renin-angiotensin system in SHRSP rats in the course of malignant hypertension at 20 weeks of age and later, could participate in raising blood pressure above the levels of the SHR and SHRSR. Considering out data and others, there are many similarities in renin profile between the SHR and its two substrains, and human essential hypertension in which PRA can be classified as low, normal or high.

Aging↗
PubMed1979

Blood pressure regulation by angiotensin in the spontaneously hypertensive rats.

Plasma renin activity (PRA) was subnormal or normal in the main strain of spontaneously hypertensive rats (SHR). PRA increased greatly in the stroke-prone substrain of SHR (SHRSP) at 20-30 weeks of age. Captopril (SQ 14,225) is an orally active angiotensin-converting enzyme inhibitor. The drug acutely decreased blood pressure moderately in SHR, and markedly in SHRSP. Participation of the renin-angiotensin system in the pathogenesis of hypertension in SHR may be limited. Etiology of hypertension in connection with renal excretory function and the central and peripheral nervous system is discussed.

Angiotensins↗
PubMed1978

Antihypertensive and antidiuretic effects of 3-hydrazino-6-[N, N-bis (2-hydroxyethyl) amino]-pyridazine (L 6150) in rats.

3-Hydrazino-6-[N,N-bis (2-hydroxyethyl)amino]-pyridazine (L 6150) has been reported as an antihypertensive vasodilator drug. We determined antihypertensive effect of L 6150 for 11 weeks in spontaneously hypertension due to clipping (CLIP). The effects of hydralazine (HZ) and ecarazine (EZ) were also determined for comparison. L 6150, HZ, and EZ showed antihypertensive effects in SHR, DOC and CLIP hypertensive rats. These drugs increased heart rate in SHR and DOC rats. In CLIP hypertension heart rate tended to be higher for 9--10 weeks after the treatments. These treatments diminished incidence of the vascular disease in DOC and CLIP. We also determined renal effects of L 6150, HZ and EZ in normal rats. These drugs decreased urine volume, and excretion of osmotically active solutes, Cl, Na, and K for 180 min after bicarbonate saline load. It is concluded that L 6150 is an antihypertensive drug with characteristics of the vasodilator in rats.

Animals↗
PubMed1978

Some frontiers in comparative studies of the renin-angiotensin system.

A prospective survey on the comparative studies of the renin-angiotensin system (RAS) was made at the final session of the Japan-U.S. Cooperative Seminar, held on November 14--19, 1977, at Jichi Medical School, Tochigi-ken, Japan. Strategies and tactics of the research have been clarified. In morphological studies, the strategy is to clarify structure of the juxtaglomerular apparatus in representative species of vetebrate classes. In chemical studies, each component of the RAS must be established in each vertebrate class. Since we now know the existence of severel new angiotensins in vertebrates, their amino-acid sequences must be determined. They must be synthesized in sufficient purity. It is necessary to establish the international purity and assay criteria for synthetic angiotensins. In comparative studies on physiological aspects, the strategy is to establish the physiological roles of the RAS in vertebrate classes. Controls of blood pressure, of aldostrone secretion, of glomerular filtration rate and tubular transport, and of drinking and intestinal absorpiton are the candidates. Physiological roles of extrarenal renin as well as renal one are interesting. A renin-like substance in the corpuscles of Stannius in the teleosts has been identified preliminarily as hypocalcin. Many frontiers exist in these fields, and one can expect fruitful contributions to research of the cardiovascular disease in humans through comparative studies of the RAS.

Amino Acid Sequence↗
PubMed1978

Influence on blood pressure of renal isografts between spontaneously hypertensive and normotensive rats, utilizing the F1 hybrids.

The F1 hybrids (F1) of spontaneously hypertensive rats (SHR) and Wistar rats (W), whose kidneys were transplanted from SHR at the age of 10 weeks and 20 weeks, showed significant elevation of blood pressure (BP) for 11 weeks after the transplantation. In F1 with W or F1 kidneys BP was decreased near to the normal level. F1 whose kidneys were transplanted from SHR or W showed low renin activity both in plasma and the kidney. It is suggested that BP of SHR is probably determined by the renal pro-hypertensive factor(s) other than renin influencing on sympathetic nerves through central nervous systems.

Animals↗
PubMed1977

Synthesis and specific pressor activity of [1-aspartic acid,5-valine,9-serine]angiotensin I ("fowl angiotensin I").

[Asp1, Val5, Ser9]angiotensin I was synthesized by Merrifield's solid-phase procedure. The dansylated derivative of this angiotensin was cochromatographed on the TLC with the dansylated angiotensin decapeptide isolated from white leghorn fowl. Either angiotensin showed identical behavior. The per mole pressor activity of the synthetic decapeptide (in rats anesthetized with pentobarbital and treated with pentolinium) as compared to mammalian angiotensins, namely, [Ile5]angiotensin I, [Val5]angiotensin I, [Ile5]angiotensin II, and [Val5]angiotensin II, was 157, 181, 114, and 85%, respectively.

Angiotensin II↗
PubMed1977

Specific pressor activity and stability of synthetic angiotensins.

Specific pressor activity of Asp1-Val5-antiotensins I and II was determined by a 4-point assay in rats against various synthetic angiotensins. Specific pressor activity of various angiotensins was also obtained from the dose-blood pressure-response (DR) curve, using a single angiotensin sample per rat. Comparison of two values showed that two angiotensins interacted in the 4-point assay, yielding a potentiation factor of 0.465-1.373. Therefore, specific pressor activity from DR curve is more reliable, because two angiotensins are not able to interact. Potency ratio on a molar basis of Asp1-IIe5-angiotensin I, Asp1-Val5-angiotensins I and II, Asn1-Val5-angiotensin II (Ciba Lot-094691), and Asp1-Val5-Ser9-angiotensin I against Asp1-IIe5-angiotensin II were 0.76, 0.91, 2.02, 0.50, and 1.39, respectively. Asp1-Val5-angiotensin II had twice the pressor activity of Asp1-IIe5-angiotensin II. Lyophylized Asp1-IIe5-angiotensins I and II kept desiccated at --20 degrees C, were stable for 27 months. Solutions of 100, 10, and 0.8 microng/ml were stable for 12, 8, and 6 months at--20 degrees C, respectively.

Angiotensin II↗
PubMed1976

Renin-angiotensin system in spontaneously hypertensive rats.

Plasma and kidney renin activities (PRA, KRA) were determined in male spontaneously hypertensive rats (SHR), the inbred strain of F27-30. Blood samples of 0.5 ml for PRA determination were obtained through a cannula inserted into the abdominal aorta without anesthesia to minimize renin release from the kidney. The PRA was 30 wk. The KRA of SHR at age 10, 20, and 30 wk was also lower, confirming a previous report. At 5 wk of age, KRA was slightly higher than that of normal controls. At 50 wk of age, PRA and KRA were significantly lower in SHR (F25) from a random-bred colony than in normal Donryu rats. It is suggested that the renin-angiotensin system is suppressed in SHR as a compensatory reaction against blood pressure elevation.

Angiotensin II↗
PubMed1976

Role of the kidney in the development and maintenance of hypertension caused by renal segmental infarction in the rat.

Utilizing the microsurgical method of transplantation in the rat, the role of the kidney in an experimental renal hypertension due to segmental renal infarction was studied. When the infarcted kidney was transplanted into the bilaterally nephrectomized recipient, hypertension developed so long as the donor kidney was transplanted within 2 weeks after infarction. With transplantation of the normal kidney into the hypertensive rat 8 weeks after infarction, BP remained high unless the infarcted kidney was removed. PRA after transplantation, or KRA of the transplanted kidneys were not correlated to the blood pressure levels. It was suggested that the infarcted kidney has the pressor mechanism, lasting for 2 weeks or more after infarction. The infarcted kidney also has the maintenance mechanism, establishing 8 weeks after infarction.

Animals↗
PubMed1975

Sympathetic nervous activity in renal and DOC hypertensive rats.

The sympathetic tone of the splanchnic nerve was quantified in renal and deoxycorticosterone (DOC) hypertensive rats under pentobarbital anesthesia by measuring equivalent stimulation frequency (ESF). ESF is the frequency of stimulus to the peripheral cut end of the nerve required to restore the preseverance level of arterial pressure. It is assumed to represent the average discharge rate of the nerve before severance. ESF was markedly increased in DOC hypertension 2 weeks after initiation of the DOC-salt treatment. It was relatively decreased after 10 weeks, but was still higher than in the controls. In renal hypertension (clipping of the left renal artery), ESF was decreased considerably 2 weeks and slightly 10 weeks after clipping. When the contralateral kidney had been removed simultaneously with clipping (clip plus uninephrectomy, ESF was not significantly changed. It is suggested that the sympathetic nervous system participates greatly in the pathogenesis of DOC hypertension but not of renal hypertension.

Animals↗