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Adrenocortical function in a new world primate, the marmoset monkey, Callithrix jacchus

GENERAL AND COMPARATIVE ENDOCRINOLOGY 2000年第1期120卷 2-7页

作者： Whitehouse, BJ Abayasekara, DRE Kings Coll London GKT Sch Biomed Sci Endocrinol & Reprod Res Grp London SE1 1UL England Univ London Royal Vet Coll Dept Vet Basic Sci London NW1 0TU England

The function of the adrenal cortex of the marmoset monkey Callithrix jacchus has been investigated. In common with other New World primates, these animals seem to be glucocorticoid resistant. Blood and adrenal glands were obtained from male and female animals under terminal pentobarbitone anesthesia. Dispersed adrenal cell preparations were obtained by treatment with collagenase and incubated with ACTH(1-24), (0.1-1000 nM) angiotensin II (0.1-1000 nM), dibutyryl cyclic AMP (dbcAMP;30-1000 muM), and forskolin (FSK;1-30 muM). Plasma cortisol levels (2113 +/- 449 ng/ml male;3858 +/- 429 ng/ml female) were found to be 10- to 20-fold higher than those quoted for Old World primates and man. The cell preparations showed no significant response to any dose of ACTH tested (0.1-1000 nM), although addition of exogenous precursor (22R-hydroxycholesterol, 2.5 muM) resulted:in an increased yield of cortisol and aldosterone. Cyclic AMP production was increased in response to forskolin (1-30 muM) but not ACTH(1-24) (1-1000 nM). In addition, dose-related responses to angiotensin II (maximal stimulation of 316 +/- 49% basal aldosterone at 100 nM angiotensin II), dbcAMP (maximal stimulation of 449 +/- 24% basal cortisol at 300 muM dbcAMP), and forskolin (maximal stimulation of 394 +/- 31% basal cortisol at 10 muM FSK) were obtained. The lack of a response in vitro to ACTH in C. jacchus cannot, therefore, be attributed either to general failure of the cells or to defects in postreceptor signaling mechanisms. The results suggest that there is a reduction in adrenal ACTH receptor number or affinity, with a high basal production rate in vivo maintaining the elevated plasma cortisol levels. (C) 2000 Academic Press.

关键词：肾上腺皮质/解剖学和组织学肾上腺皮质/药物作用肾上腺皮质/生理学促肾上腺皮质激素/投药和剂量促肾上腺皮质激素/药理学醛固酮/血液血管紧张素ⅱ/投药和剂量血管紧张素Ⅱ/药理学布拉地新/药理学狨猴属/生理学环AMP/生物合成剂量效应关系药物福司柯林/投药和剂量福司柯林/药理学氢化可的松/血液动物女(雌)性男(雄)性

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Effects of angiotensin II on visual evoked potentials in the superior colliculus of juvenile rats

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NEUROPEPTIDES 2000年第3-4期34卷 203-210页

作者： Coudé, G Marois, A Casanova, C Univ Montreal Ecole Optometrie Lab Neurosci Vis Montreal PQ H3C 3J7 Canada

There are age-related changes in the relative expression of the AT(1) and AT(2) receptors of angiotensin II (Ang Il) in brain regions such as the superior colliculus, a midbrain visual structure where both receptor subtypes are found. We investigated the effects of Ang II on gross visual activity in the colliculus of anesthetized rats aged between 15 and 35 post-natal days. Microinjection of Ang II in the superficial layers yielded a strong reduction in the amplitude of visual evoked potentials in a dose-related manner. Injection of the peptide in more ventral collicular layers did not modify the potential confirming the discrete localization of the angiotensinergic receptors in the superficial layers. Preliminary data indicated that the co-injection of Ang II with Losartan or PD 123319 yielded a partial blockade of Ang II suppressive effects, indicating that both AT(1) and AT(2) receptors are likely to be involved in mediating these responses. Overall, this study shows that the inhibitory nature of Ang II action is similar in juvenile and adult animals (Merabet et at. 1994 and Merabet et al. 1997) (C) 2000 Harcourt Publishers Ltd.

关键词：衰老血管紧张素ⅱ/投药和剂量血管紧张素Ⅱ/拮抗剂和抑制剂血管紧张素Ⅱ/药理学剂量效应关系药物诱发电位视觉/药物作用咪唑类/药理学洛沙坦/药理学微量注射吡啶类/药理学大鼠 Long-Evans 上丘/药物作用上丘/生理学动物大鼠

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Differential effects of angiotensin II on cardiorespiratory reflexes mediated by nucleus tractus solitarii a microinjection study in the rat

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JOURNAL OF PHYSIOLOGY-LONDON 1999年第1期521卷 213-225页

作者： Paton, JFR Kasparov, S Univ Bristol Sch Med Sci Dept Physiol Bristol BS8 1TD Avon England

1. The effect of microinjecting angiotensin II (ANGII) into the nucleus of the solitary tract (NTS) on both baroreceptor and peripheral chemoreceptor reflexes was compared. 2. Experiments were performed in a working heart-brainstem preparation of rat. Baroreceptors were stimulated by raising perfusion pressure and chemoreceptors were activated with aortic injections of sodium cyanide (0.025 %, 25-75 mu l). Reflex changes in phrenic nerve activity and heart rate were measured after bilateral NTS microinjection (50 nl) of ANGII (0.5-5000 fmol). 3. NTS microinjection of 5 fmol ANGII elicited a transient (28.2 +/- 6 s;mean +/- S.E.M.) bradycardia (-18 +/- 3 beats min(-1)), and decreased phrenic nerve activity cycle length and amplitude (P < 0.05). At higher doses of ANGII a similar respiratory response was seen but heart rate changes were inconsistent. 4. The baroreceptor reflex bradycardia was depressed significantly by NTS microinjections of ANGII (5-5000 fmol) in a dose-dependent manner with the reflex gain decreasing from 1.7 +/- 0.16 to 0.66 +/- 0.1 beats min(-1) mmHg(-1) (P < 0.01) at 5000 fmol. Although the chemoreceptor reflex bradycardia was depressed at a low dose of ANGII (5 fmol), all higher doses (50-5000 fmol) produced a dose-dependent potentiation of the reflex bradycardia (maximally +64 +/- 8%). The respiratory component was unaffected. The effects of ANGII on both reflexes were blocked by an ANGII type 1 (AT(1)) receptor antagonist, losartan (20 mu M). 5. The potentiating action of ANGII on the chemoreceptor reflex cardiac response was abolished by a neurokinin type 1 (NK1) receptor blocker (CP-99,994, 5 mu M) but this had no effect on the baroreceptor reflex. 6. AT(1) receptors in the NTS can depress the baroreceptor reflex bradycardia which is independent of NK1 receptors. The ANG;II effect on the cardiac component of the chemoreceptor reflex is bi-directional being inhibited at low concentrations and potentiated at higher concentrations;the latter in

关键词：血管紧张素ⅱ/投药和剂量血管紧张素Ⅱ/药理学心动过缓/病因学心动过缓/病理生理学心率/药物作用心率/生理学洛沙坦/药理学微量注射膈神经/药物作用膈神经/生理学哌啶类/药理学压力感受器/药物作用压力感受器/生理学大鼠 Sprague-Dawley 受体血管紧张素 1型受体血管紧张素 2型受体神经激肽1/拮抗剂和抑制剂反射/药物作用反射/生理学呼吸/药物作用孤束核/解剖学和组织学孤束核/药物作用孤束核/生理学 P物质/分泌动物大鼠

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Low-dose angiotensin II reduces urinary cyclic AMP excretion in spontaneously hypertensive, but not normotensive, rats: Independence from hypertension and renal hemodynamic effects of angiotensin

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JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS 1999年第1期291卷 115-123页

作者： Jackson, EK Herzer, WA Mi, ZC Vyas, SJ Kost, CK Univ Pittsburgh Med Ctr Sch Med Ctr Clin PharmacolDept Pharmacol Pittsburgh PA 15213 USA Univ Pittsburgh Med Ctr Sch Med Ctr Clin PharmacolDept Med Pittsburgh PA 15213 USA

The purpose of this study was to determine whether the greater inhibitory effect of angiotensin II (Ang II) on urinary cAMP excretion in spontaneously hypertensive rats (SHRs) compared with normotensive Wistar-Kyoto (WKY) rats is secondary to hypertension and/or renal hemodynamic changes induced by Ang II. SHRs and WKY rats were treated chronically from conception, 6 weeks of age, or 10 weeks of age (n = 8-10) with the angiotensin-converting enzyme inhibitor captopril (100 mg/kg/ day). A fourth group was not treated chronically with captopril (n = 7). At similar to 13 weeks of age, all rats were anesthetized, given a bolus of captopril (30 mg/kg), and received an intrarenal infusion of a low dose of Ang II (1 ng/min). SHRs compared with WKY rats were normotensive, mildly hypertensive, and moderately hypertensive when treated with captopril from conception, 6 weeks of age, and 10 weeks of age, respectively, whereas untreated SHRs were severely hypertensive. In SHRs, Ang II decreased urinary cAMP excretion (p <.001), and this effect was independent of duration of captopril pretreatment (p = .696). In WKY rats, Ang II did not affect urinary cAMP excretion. Low-dose Ang II caused small and similar changes in renal blood flow and glomerular filtration rate in SHRs versus WKY rats and did not affect urine volume in either strain. We conclude that the greater effect of Ang II on urinary cAMP excretion in SHRs is not due to hypertension or to the renal hemodynamic effects of Ang II, but most likely to a greater effect of Ang II on some compartment of renal adenylyl cyclase activity in SHRs.

关键词：血管紧张素ⅱ/投药和剂量血管紧张素Ⅱ/药理学血管紧张素转换酶抑制药/药理学卡托普利/药理学环AMP/尿高血压/代谢高血压/尿肾/药物作用肾/生理学大鼠近交SHR 大鼠近交WKY 动物女(雌)性男(雄)性大鼠

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EFFECT OF VASOACTIVE AGENTS ON DISTRIBUTION OF RENAL CORTICAL BLOOD-FLOW IN DOGS

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ACTA PHYSIOLOGICA SCANDINAVICA 1975年第3期95卷 318-328页

作者： TYSSEBOTN, I KIRKEBO, A UNIV BERGEN INST PHYSIOLBERGENNORWAY

The distribution of renal cortical blood flow was studied in 6 Nembutal anesthetized dogs during control periods and during infusions of adrenaline, noradrenaline, angiotensin and vasopressin. Local cortical blood flow was measured as H2 gas desaturation rate recorded polarographically by platinum electrodes in outer and inner cortex. The total renal blood flow (RBF) was measured by an electromagnetic flow meter. In the control period the outer cortical blood flow (OCF) and inner cortical blood flow (ICF) averaged 3.59 (+/- S.D. 0.85) ml/min - g and 3.23 (+/- S.D. 0.64) ml/min - g, respectively. Infusions of the various vasoactive agents caused essentially equal vascular responses. All agents caused increased local renal resistance and reduction of RBF whether given intravenously or intraarterially. The RBF could be lowered to 20-50% of initial control flow by increasing doses of vasoactive agents. OCF and ICF fell proportionately and almost to the same extent as RBF, or OCF fell slightly more than ICF. There was no evidence for patchy or zonal hypoperfusion in cortex caused by infusion of adrenaline, noradrenaline, angiotensin and vasopressin.

关键词：血管紧张素ⅱ/投药和剂量血管紧张素Ⅱ/药理学血压/药物作用肾上腺素/投药和剂量肾上腺素/药理学注射动脉内注射静脉内肾/血液供给去甲肾上腺素/投药和剂量去甲肾上腺素/药理学局部血流/药物作用刺激化学性血管升压素类/投药和剂量血管升压素类/药理学动物狗女(雌)性男(雄)性

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ANGIOTENSIN-II - RENAL LOCALIZATION IN GLOMERULAR MESANGIAL CELLS BY AUTORADIOGRAPHY

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KIDNEY INTERNATIONAL 1975年第4期8卷 245-254页

作者： OSBORNE, MJ DROZ, B MEYER, P MOREL, F HOP NECKER INSERMUNIT 7PARISFRANCE COMM ENERGIE ATOM DEPT BIOLGIF SUR YVETTEFRANCE

Angiotensin II: Renal localization in glomerular mesangial cells by autoradiography. The intrarenal localization of 3H-angiotensin II after intraaortic administration in anesthetized rats has been studied by autoradio... 详细信息

Angiotensin II: Renal localization in glomerular mesangial cells by autoradiography. The intrarenal localization of ³H-angiotensin II after intraaortic administration in anesthetized rats has been studied by autoradiography. A net concentration of radioactivity is seen in the glomeruli as compared with tubules, blood vessels and interstices. Within the glomerulus this radioactivity is predominantly localized in the mesangial cells. This mesangial concentration of radioactivity is present at 1, 2 and 5 min after ³H-angiotensin administration but is considerably diminished after 30 min. Administration of a large dose of angiotensin II or of Ile⁸-angiotensin II (a competitive inhibitor of angiotensin II) with the ³H-angiotensin II prevented the mesangial concentration of radioactivity. A similar dose of noradrenaline did not have this effect. ³H-2-8-angiotensin II-heptapeptide also showed a mesangial distribution, whereas ³H-tyrosine did not. Less mesangial radioactivity after ³H-angiotensin administration was seen in rats kept on a low salt diet for four days than in those receiving a high salt diet. The possibility of an action of angiotensin II at the level of the mesangial cells is discussed.

关键词：血管紧张素ⅱ/投药和剂量血管紧张素Ⅱ/分离和提纯血管紧张素Ⅱ/药理学放射自显影术/方法毛细血管/细胞学毛细血管/超微结构剂量效应关系药物组织学技术肾/细胞学肾小球/生理学肾小球/超微结构去甲肾上腺素/药理学放射性示踪剂钠/药理学氚动物男(雄)性大鼠

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Angiotensin II infusion exacerbates radiation nephropathy

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JOURNAL OF LABORATORY AND CLINICAL MEDICINE 1999年第3期134卷 283-291页

作者： Cohen, EP Fish, BL Moulder, JE Med Coll Wisconsin Dept Med Milwaukee WI 53226 USA Med Coll Wisconsin Dept Radiat Oncol Milwaukee WI 53226 USA

We hypothesized that angiotensin II will exacerbate radiation nephropathy in a time-specific manner, Experimental radiation nephropathy is treatable with angiotensin-converting enzyme inhibition or angiotensin II (All) receptor blockers, These interventions are particularly important between 3 and in weeks after irradiation. We therefore undertook studies in which All infusions were given at particular intervals after irradiation. Rats received total body irradiation (TBI) plus syngeneic bone marrow transplantation followed (or not) by All infusion at 200 or 400 ng/kg/min, Infusions were given from 0 to 4 or 4 to 8 weeks after irradiation, An additional group was unirradiated but infused at 800 ng/kg/min for 8 weeks. Kidney function was assessed over 26 weeks, and histology was evaluated after the animals were killed. All infusion alone did not cause azotemia, There was transient hypertension during All infusion at 800 ng/kg/min but only minor histologic injury. Irradiation caused azotemia and hypertension, which were not exacerbated by AII infusion at 200 ng/kg/min, Irradiation plus All infusion at 400 ng/kg/min from 4 to 8 weeks after TBI caused significantly greater azotemia than irradiation alone or irradiation with All infusion from 0 to 4 weeks, The blood pressure was higher in irradiated rats infused with All from 4 to 8 weeks. Arteriolar fibrinoid necrosis was a prominent feature in kidneys of rats infused with All from 4 to 8 weeks after TBI. The worsening of radiation nephropathy by All infusion from 4 to 8 weeks after irradiation strongly supports the idea of specific and sequential events in the pathogenesis of kidney failure in this model. Hypertension may play a role in these events in addition to the effect of All alone. The occurrence of arteriolar fibrinoid necrosis in the irradiated, 4-to-8-week-infused animals suggests that vascular injury during that interval determines later outcome.

关键词：血管紧张素ⅱ/投药和剂量血管紧张素Ⅱ/血液血压/药物作用骨髓移植输注胃肠外肾/药物作用肾/损伤肾/辐射效应肾炎/病因学肾炎/病理学肾炎/病理生理学辐射损伤实验性/病因学大鼠近交系肾素-血管紧张素系统/药物作用肾素-血管紧张素系统/辐射效应时间因素移植同基因动物男(雄)性大鼠

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Comparative study of ACE-inhibition, angiotensin II antagonism, and calcium channel blockade on flow-mediated vasodilation in patients with coronary disease (BANFF study)

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JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY 2000年第1期35卷 60-66页

作者： Anderson, TJ Elstein, E Haber, H Charbonneau, F Univ Calgary Dept Med Div Cardiovasc Calgary AB Canada McGill Univ Montreal PQ Canada Parke Davis & Co Ann Arbor MI USA

OBJECTIVES To determine the effect of angiotensin-converting enzyme (ACE) inhibition on brachial flow-mediated vasodilation. BACKGROUND Quinapril, an ACE inhibitor with high affinity, has been shown to improve coronary endothelial dysfunction in patients with coronary artery disease. The effectiveness of different vasoactive agents to improve human endothelial function is unknown. METHODS High resolution ultrasound was used to assess endothelium-dependent brachial artery flow-mediated vasodilation (FMD) in patients with coronary disease. We studied 80 patients (mean age 58 +/- 0.9 years) in a partial-block, cross-over design trial. Patients were randomized to one of four different drug sequences to receive quinapril 20 mg, enalapril 10 mg, losartan 50 mg or amlodipine 5 mg daily. Each patient received three drugs with a two-week washout period between treatments. The primary end point was the absolute difference in FMD after eight weeks of each study drug compared with their respective baselines analyzed in a blinded fashion. RESULTS There was mild impairment of FMD at baseline (7.3 +/- 0.6%). The change in FMD from baseline was significant only for quinapril (1.8 +/- 1%, p < 0.02). No change was seen with losartan (0.8 +/- 1.1%, p = 0.57), amlodipine (0.3 +/- 0.9%, p = 0.97) or enalapril (-0.2 +/- 0.8%, p = 0.84). No significant change in nitroglycerin-induced dilation occurred with drug therapy. The improvement in quinapril response was not seen in those with the DD ACE genotype (0.5 +/- 2.1%) but was seen in those with the ID and II genotype (3.3 +/- 1.2 and 3.2 +/- 1.9%, respectively, p = 0.03). CONCLUSION Only quinapril was associated with significant improvement in FMD, and this response is related to the presence of the insertion allele of the ACE genotype. (C) 1999 by the American College of Cardiology.

关键词：氨氯地平/投药和剂量氨氯地平/副作用血管紧张素ⅱ/投药和剂量血管紧张素Ⅱ/生理学血管紧张素转换酶抑制药/投药和剂量血管紧张素转换酶抑制药/副作用血流速度/药物作用血流速度/生理学钙通道阻滞药/投药和剂量钙通道阻滞药/副作用冠状动脉循环/药物作用冠状动脉循环/生理学冠心病/药物疗法冠心病/病理生理学药物疗法联合依那普利/投药和剂量依那普利/副作用内皮血管/药物作用内皮血管/病理生理学异喹啉类/投药和剂量异喹啉类/副作用洛沙坦/投药和剂量洛沙坦/副作用四氢异喹啉类血管舒张/药物作用血管舒张/生理学老年人女(雌)性人类男(雄)性中年人

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Angiotensin-II, renal anemia and hyporesponsiveness to recombinant human erythropoietin

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INTERNATIONAL JOURNAL OF ARTIFICIAL ORGANS 1999年第10期22卷 672-675页

作者： Schiffl, H Bergner, A Univ Munich Klinikum Innenstadt Med Klin Dept internal MedNephrol Sect D-80336 Munich Germany

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