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Biomedical subjects

M Sano

Publications and source records attributed to M Sano.

At least 613 records · Page 34Linked to original sources

Guanfacine and clonidine: the effects on adrenal medullary function in spontaneously hypertensive rats.

The effect of guanfacine on adrenal medullary function was investigated in anesthetized spontaneously hypertensive rats (SHR). This effect was compared with the clonidine-induced adrenal suppressant action. Sympathetic adrenal nerve activity and adrenal catecholamine secretion rate were determined and used for the analysis of adrenal medullary function. Intravenous administration of guanfacine (30-100 micrograms/kg) produced a decrease in both adrenal nerve activity and adrenal catecholamine secretion rate that paralleled a decrease in arterial blood pressure and heart rate. The ED50 of the guanfacine-induced decrease in adrenal nerve activity was 300 micrograms/kg, and the ED50 of clonidine was 30 micrograms/kg. This guanfacine dose produced decreases up to about 20% of the pretreatment values in both epinephrine and norepinephrine secretion rates from the adrenal medulla. Moreover, guanfacine produced a significant decrease of adrenal plasma flow rate. The adrenal plasma flow rate did not change significantly after clonidine administration. These findings suggest that the adrenal suppressant effect induced by guanfacine is predominantly due to its central action and that the vasoconstriction due to the peripheral action of guanfacine is partly related to its adrenal suppressant effect in SHR.

Adrenal Glands↗

[Effect of metoprolol on water drinking activity in Wistar Kyoto rats].

The study was undertaken to elucidate the effect of beta 1 adrenoceptor blocking agent, metoprolol, on water drinking activity in Wistar Kyoto rats (WKY). Both 7 day (10mg/kg/day) oral administration of metoprolol and propranolol did not produce any changes in the systolic blood pressure of WKY. However, metoprolol produced a significant decrease in heart rate in WKY. Neither the propranolol treated rats nor the control (non-drug group) rats showed any significant changes in heart rate. Heart rates were significantly changed in the metoprolol group as compared with the other two groups. This finding reconfirms that metoprolol has beta 1 selectivity. Drinking activity, an indicator of central nervous function, did not change after metoprolol administration. Power spectral analysis of water drinking activity did not reveal any changes in rhythm in respect to periodicity in the metoprolol group. Although water drinking activity is synchronized with urinary catecholamine and aldosterone excretion rates, urinary catecholamine and aldosterone excretion rates did not change after metoprolol administration. These findings suggest that it is the beta 1 adrenergic blocking action of a bradycardia-producing dose of metoprolol that prevented any change in water drinking behavior in WKY.

Aldosterone↗

[Effects of continuous pure tone stimulation on blood pressure, plasma norepinephrine and urinary norepinephrine concentration in stroke-prone spontaneously hypertensive rats].

The present study was undertaken to elucidate the effect of pure tone stimulation on sympathetic nerve activity in stroke-prone spontaneously hypertensive rats (SHRSP). SHRSP were exposed to a pure tone stimulation of 4 KHz at 60 dB SPL tone burst which was interrupted at a frequency of one second and continued for one hour a day for either one 10 day course period or two 10 day course periods. Over a period of 10 days, Group A received one hour-long stimulation daily. Group B received the same type of stimulation for two separate 10 day course periods and Group C did not receive any tone stimulation. Group A and Group C did not show any significant changes in blood pressure, heart rate or body weight. However, an increase in urinary norepinephrine (NE) (p less than 0.02) which returned to pretreatment levels after tone stimulation was observed in Group A. Group B showed a significant increase in blood pressure as compared with Group A (p less than 0.02): the systolic blood pressure of Group B was 233.2 +/- 36.1 mmHg; the systolic blood pressure of the sex-age matched Group A was 193.0 +/- 25.7 mmHg. Group B displayed an increase in plasma NE concentration as compared with Group A (p less than 0.05). These findings demonstrated that the summation of two 10 day course pure tone stimulations produced a larger increase in blood pressure and plasma NE concentration than one 10 day course stimulation. These increase in blood pressure and plasma NE concentration occurred via an increase in sympathetic nerve activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin II↗

[The factors affecting plasma catecholamines concentration in rats and man].

Rat and human plasma catecholamines were measured simultaneously by HPLC-THI, HPLC-ECD and REA, and the three methods were compared. An attempt was also made to determine the factors affecting the estimated value of plasma catecholamine concentration. Our study showed that: Sensitivity and reproducibility to norepinephrine and epinephrine were identical in all three methods. One advantage of the REA method is that comparatively smaller sample volumes are required to produce similar results. Plasma dopamine concentration in peripheral blood samples was determined by the HPLC-ECD rather than the HPLC-THI method. Withdrawal of 5 ml of blood produced a significant increase in norepinephrine, epinephrine and dopamine in rat plasma. The catecholamine concentration in these cases was determined by the REA method. Plasma norepinephrine concentration did not increase with age in Wistar Kyoto rats. However, plasma norepinephrine concentration increased significantly with age in stroke-prone spontaneously hypertensive rats (SHRSP). Plasma norepinephrine concentration in male SHRSP was greater than that in female SHRSP. SHRSP-plasma norepinephrine concentrations rose in parallel to increases in blood pressure. The plasma norepinephrine concentration in SHRSP with cerebral hemorrhage rose significantly as compared with the plasma norepinephrine levels in SHRSP without cerebral bleeding. Because each method of determination of plasma catecholamine concentration has both merits and demerits, selection should be determined by sample size and amount of catecholamines in the plasma samples. Factors affecting the estimated value of plasma catecholamine concentration should be taken into consideration.

Animals↗

[A chronobiological study of behavioral changes in rats].

A chronobiological study of behavioral changes in Wistar Kyoto rats (WKY), spontaneously hypertensive rats (SHR) and stroke prone spontaneously hypertensive rats (SHRSP) was undertaken. Attention was focused on changes in ambulatory activity and drinking behavior using an Ambulo-Drinkometer, the effects of centrally acting antihypertensive drugs, and the relationship between behavioral changes and humoral factors. (1) The experiment was performed during a light-dark alternation cycle. Approximately 10 days were required for rats to acclimate to new cages. (2) Using power spectral analysis, a 24 hr periodicity was dominant in both sexes of WKY and SHRSP. A 120 hr periodicity was demonstrated in female SHRSP. This long periodicity may have been due to a female sexual rhythm. (3) Ambulatory activity of WKY and SHRSP tended to decrease with age. (4) After abrupt cessation of clonidine administration, an ambulatory ultradian rhythm was demonstrated. Guanfacine treated SHR showed less change in ambulatory ultradian rhythm than clonidine treated SHR. (5) Using a Drinkometer with attached metabolic cages, drinking counts, urinary volumes, urinary aldosterone and catecholamine excretion rates were higher during the dark phase than during the light phase. It was demonstrated that analysis of rhythmicities and measurement of behavioral amplitude are both needed in the study of behavioral pharmacology.

Acclimatization↗

The suppressive effect of peritoneal exudate macrophages on production of antibody to sheep erythrocytes in vitro.

The effects of peritoneal exudate macrophages on antibody response to sheep erythrocytes (SRBC) were investigated in mice. Peritoneal exudate macrophages obtained from mice injected intraperitoneally with proteose peptone or Corynebacterium parvum 4 days earlier had stronger ability to phagocytize and degrade SRBC than normal resident macrophages. These macrophages suppressed antibody formation to SRBC in vitro as well as in vivo. This suppression was overridden by increasing the amount of SRBC and diminished completely by pretreatment of the macrophages with iodoacetate and partly by pretreatment with 2-deoxyglucose, both known to be inhibitors of phagocytosis, but not by addition of indomethacin to the in vitro culture. These results suggest that the suppression of antibody response by peritoneal exudate macrophages was due to the increased activity of these cells as scavenger cells, resulting in a reduced amount of effective antigenic stimulation, and that it was not mediated by a prostaglandin-dependent mechanism. The scavenger function of these macrophages may be due to Ia-negative macrophages.

Animals↗

Inhibition of adenylate cyclase by a membrane protein from rat cerebrum.

The inhibitor protein of adenylate cyclase was partially purified from detergent-extract of rat brain. The inhibition occurred without lag phase. Calmodulin, GTP, guanyl 5'-yl imidodiphosphate (Gpp (NH) p) and forskolin did not change the inhibition, but activities stimulated by NaF or Mn2+ were more resistant for the inhibition. The inhibitor might include an essential sulfhydryl group.

Adenylyl Cyclase Inhibitors↗

Determination of 20 alpha-hydroxy-9 beta,10 alpha-pregna-4,6-dien-3-one in plasma by selected ion monitoring.

A selected ion monitoring (SIM) method has been devised for the determination of metabolites of dydrogesterone, 20 alpha-hydroxy-9 beta,10 alpha-pregna-4,6-dien-3-one (DHD) and DHD glucuronide, in plasma. Using testosterone as an internal standard (IS), DHD and IS were extracted with n-hexane and were purified by means of magnesium oxide column chromatography. The purified DHD and IS were converted to their diheptafluorobutyryl derivatives (DHD diHFB and testosterone diHFB) with heptafluorobutyric anhydride in acetone for analysis by SIM. SIM was carried out with a 2% OV-17 column (1 m) at 230 degrees C by monitoring the molecular ions of the derivatives (m/z 706 for DHD diHFB, m/z 680 for testosterone diHFB). DHD was determined from a calibration curve using a peak area method. The determination limit of the devised method was about 5 ng DHD per ml of plasma and the reproducibility was within +/- 6% of the coefficient of variation for 30 ng of DHD per ml of plasma or above.

Dydrogesterone↗