PubMed Health⌕ Search

Biomedical subjects

T X Watanabe

Publications and source records attributed to T X Watanabe.

69 records · Page 4Linked to original sources
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↗
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↗
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↗
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

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↗
PubMedDate not supplied

Solution synthesis of calciseptine, an L-type specific calcium channel blocker.

Calciseptine, an L-type specific calcium channel blocker consisting of 60 amino acid residues with four intramolecular disulfide bonds, was synthesized by the solution procedure applying our maximum protection strategy. The recently developed solvent systems used were a mixture of chloroform or dichloromethane and trifluoroethanol; they were useful for the synthesis of slightly soluble protected peptides. After removal of all the protecting groups by our two-step HF procedure followed by treatment with mercuric acetate, the peptide was folded into its native form by air oxidation, in which redox reagents were necessary to accelerate the correct disulfide bond formation. The product was purified to homogeneity and found to block contractions of the rat thoracic aorta induced by 40 mM K+ with the same potency as that of the natural product. In addition, this peptide was found to block contractions of various rat smooth muscle preparations as well as increase in cytosolic free calcium concentration induced by a high concentration of extracellular K+.

Amino Acid Sequence↗
PubMedDate not supplied

Solution synthesis of mu-conotoxin GIIIB: optimization of the oxidative folding reaction.

mu-Conotoxin GIIIB, a skeletal muscle sodium channel specific blocker, was synthesized by the solution procedure. The whole molecule, which is composed of 22 amino acid residues including six cysteinyl and three trans-4-hydroxy-L-prolyl residues, was constructed from three segments. After removal of all protecting groups, the hexa-SH peptide was subjected to an oxidative folding reaction at a peptide concentration of 1 x 10(-5) M. Three major products 1, 2 and 3 were formed in a ratio of 1:4:3. Determination of the disulfide structures in each product revealed them to be disulfide isomers, with similar connectivities in the latter two. Study of the biological activities of the three products in mice indicated that only product 1, which is a minor component, has the same potency as the natural product. Analysis of the folding process at a peptide concentration of 1 x 10(-5) M showed that the disulfide bond between Cys10 and Cys15 was initially formed, thus leading to the predominant generation of products 2 and 3. The optimal conditions for the formation of product 1 (mu-conotoxin GIIIB) were obtained by increasing the peptide concentration in the oxidation reaction mixture or by using redox reagents, both of which functioned as promoters for the thiol-disulfide exchange reaction of the mismatched disulfide bond between Cys10 and Cys15.

Amino Acid Sequence↗