• The Korean Journal of Physiology
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• 제27권2호
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• pp.217-225
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• 1993

The role of endogenous brain angiotensin ll (Ang ll) in mediating the cardiovascular and vasopressin responses to hemorrhage was assessed in conscious spontaneously hypertensive rats (SHR), and normotensive Wistar-Kyoto (WKY) rats. Artificial cerebrospinal fluid (aCSF) with or without losartan (DuP 753), a specific Ang ll receptor subtype I $(AT_1)$ antagonist and saralasin, a combined $AT_1/AT_2$ antagonist was administered into the cerebral lateral ventricle. Hemorrhage was performed at a rate of 3 ml/kg/min far 5 min. Intracerebroventricular administration of losartan and saralasin had no effect on the basal blood pressure. However, in response to acute hemorrhage, central Ang ll antagonists produced a remarkably greater fall in blood pressure, a reduced tachycardia, and an enhanced renin release compared with the aCSF control experiment in SHR, but effected no significant change in WKY rats. Central Ang ll-blocked SHR showed significantly lower blood pressure and heart rate during the recovery period than the aCSF control rats. Vasopressin release tallowing the hemorrhage was attenuated by icv Ang ll antagonists: the effect was more pronounced in SHR than in WKY rats. Centrally administered losartan and saralasin produced remarkably similar effects on the cardiovascular function and vasopressin responses to hemorrhage. These data suggest that brain Ang ll acting primarily through AT, receptors plays an important physiological role in mediating rapid cardiovascular regulation and vasopressin release in response to hemorrhage especially in Hypertensive rats.

• 대한약리학회지
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• 제27권1호
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• pp.21-31
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• 1991

미주신경절단 가토에서 니코틴성약물인 nicotine과 DMPP뿐아니라 무스카린성 약물인 muscarine과 bethanechol은 측뇌실내 투여로 모두 혈압상승작용을 나타냈다. Nicotine과 DMPP에 대한 승압반응은 측뇌실내 mecamylamine처리로 현저히 감약되었으나 측뇌실내 pirenzepine처리에 의해서는 영향받지 않았고, muscarine과 bethanechol에 대한 승압반응은 pirenzepin에 의해서는 억제되나 mecamylamine에 의해서는 영향받지 않았다. 이는 뇌내의 니코틴성 수용체 및 무스카린성 수용체가 모두 혈압상승에 관여함을 가리키고 있다. Nicotine과 muscarine에 대한 승압반응은 regitine, reserpine, enalapril, saralasin, SK&F-100273, regitine과 enalapril, regitine과 saralasin의 정맥내 처리에 의해서는 억제되지 않았으며 nicotine에 대한 승압반응은 regitine과 SK&F-100273 두약물의 병용처리에 의해서 억제되었고 muscarine에 의한 승압반응은 regitine, enalapril과 SK&F-100273의 세가지 약물의 병용처리에 의해서만 억제되었다. Nicotine이나 muscarine에 의한 혈압상승상태에서 정맥내 regitine의 투여는 혈압하강을 일으켰으나 enalapril이나 SK&F-100273은 혈압하강을 일으키지 못하였다. Enalapril은 regitine처리나 regitine과 SK&F-100273병용처리 가토에서 nicotine에 의해 상승된 혈압을 하강시키지 못하였으나 SK&F-100273은 regitine처리 가토에서 nicotine에 의한 상승된 혈압을 하강시켰다. Enalapril은 이러한 SK&F-100273의 할압하강작용을 강화시키지 못하였다. Enalapril은 regitine 처리 가토에서 muscarine에 의하여 상승된 혈압은 하강시키지 못하였으나, regitine과 SK&F-100273병용처리 가토에서 muscarine에 의해 상승된 혈압은 하강시켰다. SK&F-100273은 regitine처리 가토에서 muscarine에 의해 상승된 혈압을 하강시키지 못했으나 regitine과 enalapril병용처리 가토의 상승된 혈압은 하강시켰다. 이상의 성적은 뇌실내 nicotine에 의한 혈압상승에는 말초에서 교감신경계와 vasopressin이 관여하며 muscarine에 의한 혈압상승에는 교감신경계, vasopressin 및 angiotensin계가 관여함을 시사하고 있다. Regitine의 정상 가토 혈압하강작용은 enalapril이나 SK&F-100273의 단독처리에 의해서는 영향받지 않았으나 이 두약물을 병용처리시에는 유의하게 강화되었고, 이는 가토 동맥압의 유지에 교감신경, renin-angiotensin 및 vasopressin계가 관여함을 시사하고 있다.

• The Korean Journal of Physiology
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• 제26권1호
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• pp.69-74
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• 1992

Central cardiovascular effects of bradykinin were examined in anesthetized normotensive (NTR) and 2-kidney, 1 clip Goldblatt hypertensive rats (GHR). Bradykinin ($0.5{\sim}10nmol$) was administered into the right lateral cerebral ventricle, while blood pressure and heart rate (HR) were continuously monitored. In both NTR and GHR, intracerebroventricular bradykinin produced a dose dependent increase in mean arterial pressure (MAP) without significant changes in HR. GHR were more sensitive in the pressor response than NTR. The pressor response to bradykinin was attenuated by treatment with hexamethonium (2.5mg/kg/min, IV) or phentolamine (2mg/kg, IV) in both NTR and GHR. Reserpine treatment (2mg/kg/day, intramuscularly,2 days) did not affect the central pressor effect of bradykinin in NTR but it attenuated the pressor effect in GHR. Pretreatment with indomethacin (10mg/kg, intraperitoneally) or saralasin ($20{\mu}g$/kg/min, IV) was without effects on the pressor response to bradykinin. These results indicate that the central pressor effect of bradykinin is, at least in part, due to excitation of the autonomic nervous activity. Mechanisms other than the enhanced sympathetic nervous activity ran. not be ruled out, However. It is also suggested that the sensitivity to bradykinin is increased in the GHR.

• The Korean Journal of Physiology
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• 제28권2호
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• pp.197-202
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• 1994

The present study was aimed to determine if endogenous L-arginine-nitric oxide (NO) pathway has central, rather than peripheral, mechanisms in blood pressure regulation. Arterial blood pressure and heart rate responses to acute inhibition of the t-arginine-NO pathway were examined in rats anesthetized with thiopental (50 mg/kg, IP). An intracerebroventricular (ICV) cannula was placed in the left lateral ventricle. The right femoral artery was cannulated to measure arterial blood pressure and the vein to serve as an infusion route. $N^G-nitro-L-arginine$ methyl ester (L-NAME) was infused either intracerebroventricularly or intravenously. ICV infusion $(1.25\;{\mu}L/min)$ of L-NAME $(20\;or\;100\;{\mu}g/kg)$ per minute for 60 min) increased the mean arterial pressure and heart rate. Plasma renin concentrations(PRC) were significantly lower in L-NAME-infused group than in the control. L-Arginine $(60\;{\mu}g/min,\;ICV)$ prevented the pressor response to ICV L-NAME. The pressor response was not affected by simultaneous intravenous infusion of saralasin, but was abolished by hexamethonium treatment. Intravenous infusion $(40\;{\mu}L/min,\;10{\sim}100\;{\mu}g/kg\;per\;minute\;for\;60\;min)$ also increased blood pressure, while it decreased heart rate. These results indicate that endogenous L-arginine-NO pathway has separate central and peripheral mechanisms in regulating the cardiovascular function. The central effect may not be mediated via activation of renin-angiotensin system, but via, at least in part, activation of the sympathetic outflow.