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Biomedical subjects

M Kanazawa

Publications and source records attributed to M Kanazawa.

At least 235 records · Page 13Linked to original sources
PubMed1990

Role of bradykinin in the regulation of blood pressure and renal blood flow in DOCA-salt hypertensive rats.

We examined the role of bradykinin in the onset and/or the maintenance of blood pressure and renal blood flow in deoxycorticosterone acetate (DOCA)-salt hypertensive rats by using a competitive antagonist of bradykinin [Arg-Pro-Hyp-Gly-Thi-Ser-Dphe-Thi-Arg; Hyp, L-4-hydroxyproline; Thi, beta-(2-theinyl-L-alanine)]. The intravenous injection of the bradykinin antagonist (25, 50 and 100 micrograms) produced an increase in mean arterial pressure in all rats treated with tap water, 1% NaCl and DOCA + 1% NaCl. However, the magnitude of the increase in mean arterial pressure was significantly lower in the DOCA-hypertensive rats than in the two groups of rats drinking tap water and 1% NaCl after 4 and 6 weeks, but there was no significant difference after 2 weeks. The bradykinin antagonist induced a decrease in renal blood flow in all rats. However, the extent of the fall in renal blood flow was reduced in the DOCA-hypertensive rats compared with the control rats drinking tap water. These results suggest that endogenous bradykinin is depressed in the established phase of hypertension in DOCA-hypertensive rats. It is also suggested that endogenous bradykinin may counteract the elevation of vascular resistance in the early stages of this model.

Animals↗
PubMed1990

Depressor mechanism of enalapril in rats made hypertensive by norepinephrine or vasopressin.

We evaluated the antihypertensive mechanism of enalapril, a long-lasting inhibitor of angiotensin-converting enzyme, in rats made hypertensive by chronic infusion of norepinephrine or vasopressin. The hypertensive effect of norepinephrine (1.8 mg/kg/day intraperitoneal (i.p.] or vasopressin (7.2 U/kg/day i.p.) was completely abolished by simultaneous administration of enalapril (6 mg/kg/day i.p.). The antihypertensive effect of enalapril was not reversed by simultaneous administration of subpressor doses of angiotensin II (36 and 100 micrograms/kg/day i.p.). However, the hypertensive effects of angiotensin II at pressor doses (600 and 900 micrograms/kg/day i.p.) in enalapril-infused rats were not different from those in vehicle-infused rats. These results indicate that the hypotensive effect of enalapril may in part depend on a reduced sensitivity of the vasculature to norepinephrine and vasopressin, independent of inhibition of angiotensin II formation.

Angiotensin II↗
PubMed1990

Calcium channel blockers reverse the sustained elevation of blood pressure induced by chronic infusion of endothelin in conscious rats.

To determine whether endothelin could act as a circulating hormone in the regulation of blood pressure and sodium-water excretion, we assessed the chronic effects of synthetic endothelin on systolic blood pressure, urine volume and urinary sodium excretion in conscious rats, and also evaluated the effects of benidipine or nilvadipine, newly developed calcium channel blockers, in rats infused chronically with synthetic endothelin. Continuous infusion of endothelin at a rate of 60 micrograms/kg/day into the jugular vein via osmotic minipumps induced a significant increase in systolic blood pressure, but did not induce any significant changes in urine volume and urinary sodium excretion, compared to those in vehicle-infused rats. On the contrary, the infusion of endothelin at a rate of 6 micrograms/kg/day did not induce any significant changes in systolic blood pressure, urine volume and urinary sodium excretion, compared to those in vehicle-infused rats. When 6 mg/kg/day of benidipine or 10 mg/kg/day of nilvadipine was administered simultaneously with 60 micrograms/kg/day of endothelin, the systolic blood pressure rose on Day I to only 137.0 +/- 2.4 mmHg (p less than 0.05) and 119.7 +/- 5.9 mmHg (p less than 0.05) compared to the rise to 163.8 +/- 4.7 mmHg when endothelin alone was infused. The antihypertensive effect of benidipine or nilvadipine was sustained for the entire experimental period and was not associated with any significant changes in urine volume and urinary sodium excretion. The present results suggest that endothelin can act as a circulating hormone and might be involved in the regulation of blood pressure.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Effects of digoxin on blood pressure responses to norepinephrine, angiotensin II and vasopressin in conscious rats.

To investigate the interaction of cardiac glycosides with vasoconstrictors, we examined the effects of short term treatment with the cardiac glycoside digoxin (6 mg/kg/day, i.p., for 6 days) in rats made hypertensive by chronic infusion of norepinephrine (NE), angiotensin II (A II) or vasopressin (VP). When digoxin was administered simultaneously with NE at 1.8 mg/kg/day (i.p.) by use of osmotic minipumps in conscious rats, systolic blood pressure decreased to 120 +/- 3 mmHg on Day 1 whereas it rose to 148 +/- 2 mmHg in rats given NE alone (p less than 0.01). The antihypertensive effect of digoxin was sustained for the entire experimental period and was not associated with any change in urinary sodium excretion. When the same dose of digoxin was administered simultaneously with A II at 900 micrograms/kg/day (i.p.) in conscious rats, systolic blood pressure rose to a greater extent than in those given A II alone. The administration of digoxin had no effect on the blood pressure elevation induced by chronic infusion of VP at a rate of 7.2 U/kg/day (i.p.). It is concluded that short term treatment with digoxin has a variety of effects on blood pressure in rats; pressor, depressor, or is no effects depending upon vasoconstrictor used.

Angiotensin II↗
PubMed1990

Failure to visualize bilateral adrenal glands in a patient with primary aldosteronism.

Failure to visualize either adrenal gland by adrenal imaging was experienced in a patient with biochemical evidence of primary aldosteronism. Visualization of the adrenal glands was not possible after the administration of ACTH-Z (1 mg/day) for 3 days. The administration of ACTH and dexamethasone elicited an increase in blood pressure. Although the reason for this failure to visualize the adrenal glands by scanning and for the rise in blood pressure brought on by ACTH and dexamethasone remain unclear, we think that the case herein reported is a rare type of primary aldosteronism.

Adosterol↗
PubMed1990

[A case of brain metastasis from breast cancer responding to chemoendocrine therapy].

Brain metastasis is one of the most critical metastatic lesion on the treatment of breast cancer. We reported a case with brain metastasis from breast cancer responding to chemoendocrine therapy. The patient was 71 years old female complaining gait disturbance. Solitary brain metastasis and multiple bone metastases of breast cancer were diagnosed by CT scan and bone scintigram. Standard radical mastectomy was done. Estrogen receptor was proved to be positive in both of the tumor and metastatic lymph node. Tamoxifen and UFT were administered as chemoendocrine therapy. Complete response of brain metastasis was recognized in CT scan and gait disturbance was complete recovered two months after the treatment. She is now living well.

Aged↗
PubMed1990

[Effects of antihypertensive therapy on the renal function in spontaneously hypertensive rats (SHR) with renal ablation].

To determine whether pharmacological control of blood pressure could affect the renal function and its deterioration in SHR with renal ablation, we studied effects of oral administration of captopril (50 mg/kg/day) and ramipril (10 mg/kg/day), angiotensin converting enzyme inhibitors (ACEI), nilvadipine (10 mg/kg/day) and benidipine (3-6 mg/kg/day), calcium channel blockers (CCB), and indapamide (10 mg/kg/day), a non-thiazide diuretic, for 2 and 12 weeks on systolic blood pressure (SBP), blood urea nitrogen (BUN) and serum creatinine (Scr), endogenous creatinine clearance (Ccr), and urinary protein excretion (UP) in SHR subjected to 5/6 nephrectomy a week before. Three weeks after the surgery, SBP (mmHg) in the untreated group was 253 +/- 8.9 (n = 11), captopril group 156 +/- 8.9 (n = 7, p less than 0.05), ramipril group 176 +/- 12 (n = 7, p less than 0.05), nilvadipine group 146 +/- 8.8 (n = 7, p less than 0.05), and benidipine group 197 +/- 8.5 (n = 7, p less than 0.05). Monotherapy with indapamide (206 +/- 4.8, n = 7, p less than 0.05) induced only a slight decrease in the SBP. Thirteen weeks after the surgery, SBP in the untreated group was 270 +/- 6.9 (n = 14), in the captopril group 191 +/- 4.8 (n = 7, p less than 0.05), in the ramipril group 160 +/- 9.5 (n = 7, p less than 0.05), in the nilvadipine group 177 +/- 13.2 (n = 7, p less than 0.05), and in the benidipine group 150 +/- 4.9 (n = 7, p less than 0.05). BUN was lower in the captopril and nilvadipine groups but not in the other treatment groups compared with the untreated group. Scr was lower in the ACEI groups. Ccr was higher in the ACEI and benidipine groups. UP was lower in all treatment groups. These results indicate that the similar reduction of SBP by ACEI and CCB has the potential to preserve renal function and to lessen renal damage in this model. Furthermore, they also suggest that ACEI have the potential to ameliorate renal function in this model. However, it remains to be determined why, despite the similar effects on SBP, deterioration of renal function in this model was prevented only by treatment with the ACEI, but not with the CCB.

Animals↗
PubMed1989

Role of renal kallikrein in the regulation of blood pressure in the rat remnant kidney model of chronic renal failure.

We studied urinary excretion of active and inactive kallikrein every day for 3 weeks in spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY) subjected to 5/6 nephrectomy (5/6), 1/2-nephrectomy (1/2) or sham-operation (Sham). We determined urinary active and inactive kallikrein by measuring kallikrein activity using a kininogenase assay before and after treatment with trypsin (200 micrograms/ml). In the SHR group, blood pressure was significantly elevated in 5/6-animals as compared with 1/2 or sham, whereas in the WKY group blood pressure was not changed after either operation. Urinary active and total kallikrein excretion were decreased in 5/6-SHR to 34% and 59%, respectively, as compared with values of sham-SHR, and in 1/2-SHR to 70% and 70%, respectively. Similarly, they were also decreased in 5/6-WKY to 36% and 55%, respectively, as compared with values of sham-WKY. In 1/2-WKY urinary active kallikrein excretion was decreased to 88% as compared with the value of sham-WKY, but urinary total kallikrein excretion was not different from that of sham-WKY. Thus, the suppressed renal kallikrein activity due to reduced renal mass was not associated with any significant change in blood pressure in WKY, although it induced an elevation of blood pressure in SHR. These results indicate that the decreased production of renal active kallikrein may not play a significant role in the regulation of blood pressure in the rat remnant kidney model of chronic renal failure. In addition, it is suggested that the elevation of blood pressure in this model of SHR may be due to other factors than renal kallikrein.

Animals↗
PubMed1989

Role of renal kallikrein in the increased fractional sodium excretion in the rat remnant kidney model of chronic renal failure.

To assess the potential role of renal kallikrein-kinin system in enhancing sodium excretion per nephron in chronic renal failure, we studied urinary excretion of active and inactive kallikrein for 3 weeks in Wistar-Kyoto rats subjected to 5/6 nephrectomy (5/6), 1/2 nephrectomy (1/2) or sham operation (Sham). We determined urinary active and inactive kallikrein by measuring kallikrein activity using a kininogenase assay before and after treatment with trypsin (200 micrograms/ml). Fractional sodium excretion was significantly increased in 5/6-rats as compared with 1/2- or sham-rats. On the contrary, urinary active kallikrein excretion per nephron was not different in the three models whereas a significant rise in urinary inactive kallikrein excretion per nephron was found in 5/6-rats as compared with 1/2- or sham-rats. Urinary total kallikrein excretion per nephron was significantly increased in 5/6-rats as compared with sham-rats. In addition, no correlation was found between fractional sodium excretion and urinary active kallikrein excretion corrected for creatinine clearance (Ccr) in 5/6-rats. These results indicate that decreased excretion of renal active kallikrein may not play a significant role in the increased sodium excretion per nephron in the rat remnant kidney model of chronic renal failure. Furthermore, it is suggested that in this model of rat there might be impaired production of renal active kallikrein although its exact mechanism remains to be determined.

Animals↗
PubMed1989

PGE2 synthesis in cultured renal papillary collecting tubule cells from young and aged spontaneously hypertensive rats.

To investigate whether altered renal medullary prostaglandin (PG) synthesis is involved in the development of hypertension in spontaneously hypertensive rats (SHR), we compared the capacity of PGE2 synthesis in cultured renal papillary collecting tubule cells from young (4-week-old) and aged (16-week-old) SHR and control Wistar-Kyoto rats (WKY). Basal levels of PGE2 synthesis were lower in young SHR cells than in WKY cells (p less than 0.001). Arachidonic acid-stimulated PGE2 synthesis, however, had a slight tendency to be higher in SHR cells than in WKY cells. Bradykinin- and A23187-stimulated PGE2 synthesis were similar in both strains. Basal levels of cyclic AMP were also lower in young SHR cells than in WKY cells (p less than 0.001), but the cAMP response to exogenous PGE2 was equal between the strains. In papillary collecting tubule cells from aged rats, basal levels of PGE2 and cyclic AMP as corrected for cellular protein were significantly lower than those in young rats, but there was no difference between the strains. Urinary excretion of PGE2 and thromboxane B2 was equal in aged SHR and WKY. These results suggest that papillary collecting tubule of young SHR and WKY may differ in the metabolism of PGE2 and cyclic AMP. This difference may be attributed to the possible defect in arachidonate availability in SHR.

1-Methyl-3-isobutylxanthine↗
PubMed1989

Effect of cytochalasin D on acinar cell structure and secretion in rat parotid salivary glands in vitro.

Cytochalasin D, a microfilament disrupting agent, considerably inhibited isoproterenol-stimulated amylase release from enzymatically dispersed parotid acini. Histologically cytochalasin D caused a loss of microvilli lining acinar lumina and luminal enlargement. Nearly empty vacuoles appeared near the luminal and lateral surface, and the membrane bordering on the vacuoles was often continuous with the plasma membrane. Therefore, the vacuolization probably resulted from an elongation of the membrane lining the lumen. Fluorescence staining with rhodamine-phalloidin showed that cytochalasin D caused disruption of microfilaments. When stimulating the cytochalasin D-treated cells with isoproterenol, the number of secretory granules in the cytoplasm diminished markedly and secretory material was observed in the vacuoles, indicating that inhibition of amylase release by cytochalasin D is not due to blocking of exocytosis but to the retention of amylase discharged into vacuoles. These findings suggest that microfilaments are essential in maintaining the parotid acinar structure but do not play a direct part in the movement of secretory granules and their fusion with the luminal membrane.

Actin Cytoskeleton↗
PubMed1989

The role of calmodulin in rat parotid amylase secretion: effects of calmodulin antagonists on secretion and acinar cell structure.

Using dispersed rat parotid cells, the effects of three calmodulin antagonists, trifluoperazine (TFP), N-(6-aminohexyl)-5-chloro-1-naphthalensulfonamide (W-7), and N-(6-aminohexyl)-1-naphthalenesulfonamide (W-5), on amylase release and acinar cell structure were examined. TFP and W-7 strongly inhibited both isoproterenol (ISO)- and dibutyryl cyclic AMP-stimulated amylase release at a concentration of 50 or 100 microM, while W-5, a weak calmodulin antagonist, had only little effect. Cyclic AMP level was markedly elevated by ISO even in the presence of TFP or W-7. These results indicate that the calmodulin antagonists affect amylase release at steps distal to cyclic AMP metabolism. Electron micrographs demonstrated that treatment of parotid cells with either TFP or W-7 caused a loss of luminal microvilli and surface folds. When cells were stimulated by ISO in the presence of TFP or W-7, the enlarged lumina did not recover to their original size and the discharged secretory material was retained in the lumina. Numerous secretory granules remained in the acinar cytoplasm. W-5 affected the acinar cell structure only a little. These observations lead to the assumption that TFP and W-7 interfered with the normal functions of the cytoskeletal system. It is proposed that calmodulin may be involved in the exocytosis of parotid amylase through the regulation of the cytoskeletal system.

Amylases↗
PubMed1989

Prognostic value of low-level exercise testing in patients with myocardial infarction.

The prognostic value of low-level exercise testing (EXT) before hospital discharge was assessed in 111 patients with uncomplicated acute myocardial infarction (AMI). Of 111 patients, 94 were followed for 1 year after AMI to find that 22 carried a poor prognosis: reduction in duration of EXT (6 patients), postinfarction angina (2 patients), congestive heart failure (3 patients), coronary bypass graft surgery (7 patients) and reinfarction (4 patients). The prognosis was poor in 3.7% of 54 patients who tolerated exercise for 721 seconds or longer (4.2 METs) and 50% of 40 patients tolerating it no longer than 720 sec (p less than 0.0001). Of 22 patients who turned out to be carriers of a poor prognosis, 12 (54.5%) had an ST segment change during EXT, but 10 of the 12 patients were asymptomatic. Our results suggest that reduction in duration of exercise and asymptomatic ST segment changes during EXT provide important clues to establishing the short-term prognosis of AMI.

Adult↗
PubMed1989

Acute and chronic effects of synthetic atrial natriuretic factor on blood pressure and sodium excretion in spontaneously hypertensive rats.

To assess possible roles of atrial natriuretic factor (ANF) in the regulation of blood pressure in spontaneously hypertensive rats (SHR), we performed two series of experiments. First, we studied acute hypotensive, natriuretic and diuretic effects of ANF in pentobarbital-anesthetized SHR and age-matched Wistar-Kyoto rats (WKY). A synthetic ANF of 25 amino acid residues was intravenously administered as a bolus at doses of 0.1, 1.0, 2.5 and 5.0 micrograms/kg. In SHR group, a significant decrease in mean arterial pressure (MAP) was observed at a dose of 1.0 micrograms/kg, and the decrease was dose-dependent. On the other hand, in WKY group, the hypotensive effect of ANF was not observed until a dose of 5.0 micrograms/kg. The diuretic and natriuretic effects of ANF were observed at a dose of 2.5 micrograms/kg in SHR and 5.0 micrograms/kg in WKY, respectively. Second, we also studied chronic effect of ANF on the development of hypertension in 6-week-old SHR. The SHRs, on regular diet or given 1% NaCl solution for drinking, were continuously infused into the jugular vein by osmotic minipumps with ANF (15, 75 and 150 micrograms/kg/day) or vehicle (physiological saline) as controls for up to 14 days. ANF at a dose of 150 micrograms/kg/day attenuated transiently the development of hypertension in the sodium-loaded SHR. However, the blood pressure returned to control levels by day 5. ANF at doses of 15 and 75 micrograms/kg/day did not affect the development of hypertension. In SHR on regular diet, ANF at a dose of 150 micrograms/kg/day did not affect the development of hypertension. In addition, ANF did not induce any significant changes in urine volume, fluid intake, and urinary excretion of sodium and potassium in SHR, whether they were sodium-loaded or not, when compared to those in vehicle-infused SHR. These results indicate that there may be a significant difference in the sensitivity to diuretic, natriuretic and hypotensive actions of ANF between SHR and WKY. Moreover, it is suggested that ANF may play significant roles by its vascular effect at the early stage of development of hypertension in sodium-loaded SHR.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Blood pressure and renal responses to synthetic rat atrial natriuretic factor in deoxycorticosterone acetate-salt hypertension.

To assess possible roles of atrial natriuretic factor (ANF) in the regulation of blood pressure in deoxycorticosterone acetate (DOCA)-salt hypertensive rats, we performed two series of experiments. First, we studied acute hypotensive, and natriuretic and diuretic effects of ANF in pentobarbital-anesthetized DOCA-salt hypertensive rats and age-matched controls. A synthetic rat ANF was intravenously administered as a bolus at doses of 0.5, 2.5 and 5.0 micrograms/kg. In DOCA-salt rats, a significant decrease in mean arterial pressure was observed at a dose of 5.0 micrograms/kg, whereas at a dose of 2.5 micrograms/kg in control rats. On the other hand, the diuretic and natriuretic effects of ANF were observed at a dose of 2.5 micrograms/kg in DOCA-salt rats and 5.0 micrograms/kg in control rats. Second, we examined chronic effect of ANF on the development of hypertension in DOCA-salt rats. The DOCA-salt rats, given 1% NaCl solution for drinking, were continuously infused with ANF (15, 75 and 150 micrograms/kg/day) or vehicle (physiological saline) into the jugular vein by osmotic minipumps for up to 14 days. In DOCA-salt treated rats, ANF at doses of 75 and 150 micrograms/kg/day attenuated significantly the development of hypertension, although at a dose of 15 micrograms/kg/day did not. The hypotensive effect of ANF was sustained throughout the experimental period and the effect of ANF at a dose of 150 micrograms/kg/day was more prominent than that of this peptide at a dose of 75 micrograms/kg/day. ANF did not induce any significant changes in urine volume, fluid intake and urinary excretion of sodium and potassium in DOCA-salt rats when compared to those in vehicle-infused DOCA-salt rats. These results indicate that DOCA-salt rats are more sensitive to ANF in diuretic and natriuretic effects, and less sensitive to ANF in hypotensive effect compared to control rats. Moreover, it is suggested that ANF can affect the regulation of blood pressure by its vascular effect in the development of hypertension in DOCA-salt rats.

Animals↗
PubMed1989

The effect of atrial natriuretic peptide on cytosolic free calcium in cultured vascular smooth muscle cells.

Effect of atrial natriuretic peptide (ANP) on cytosolic free calcium [( Ca2+]i) was studied in monolayers of cultured vascular smooth muscle (VSM) cells loaded with a fluorescent calcium indicator, fura-2. Vasoconstrictive hormones, angiotensin II (AII) and Arg8-vasopressin (AVP) induced initial rapid rises in [Ca2+]i, followed by sustained elevation of [Ca2+]i. ANP (Atriopeptin III 10(-8) M) decreased both the resting level and the sustained elevation of [Ca2+] i induced by AII and AVP. ANP also decreased the rise in [Ca2+]i induced by high potassium (K+) depolarization. AVP-induced initial rapid rise in [Ca2+]i was not inhibited by ANP in the presence or absence of the phosphodiesterase inhibitor, isobutylmethylxanthine 0.1 mM, which has been shown to fully enhance ANP-induced cyclic GMP accumulation. On the other hand, a calcium antagonist, nicardipine, inhibited the high K+-induced rise in [Ca2+]i, whereas it had no effect on not only initial but also sustained rises in [Ca2+]i induced by AVP or AII. These results suggest that ANP has an ability to decrease [Ca2+]i not through inhibition of voltage-sensitive calcium channels, and that neither ANP nor ANP-induced cyclic GMP may affect initial hormone-induced rise in [Ca2+]i. In conclusion, an ability to decrease [Ca2+]i is implicated in ANP-induced relaxation of VSM.

1-Methyl-3-isobutylxanthine↗