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Contribution of endogenous nitric oxide to basal vasomotor tone of peripheral vessels and plasma B-type natriuretic peptide levels in patients with congestive heart failure

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JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY 2000年第5期36卷 1605-1611页

作者： Ishibashi, Y Shimada, T Sakane, T Takahashi, N Sugamori, T Ohhata, S Inoue, S Katoh, H Sano, K Murakami, Y Hashimoto, M Shimane Med Univ Dept Internal Med 4 Izumo Shimane 6938501 Japan Shimane Med Univ Dept Physiol Izumo Shimane 6938501 Japan

OBJECTIVES We examined whether a relationship exists between the vasoconstrictive response to endogenous nitric oxide (NO) synthesis inhibition and the severity of heart Failure in patients with congestive heart failure (CHF). BACKGROUND Controversy exists as to whether the vasoconstrictive response to NO synthesis inhibition in patients with CHF is comparable to that in normal subjects or is enhanced. METHODS Forearm blood flow (FBF) and calculated forearm vascular conductance (FVC) were obtained using plethysmography before and after administration of the NO synthesis inhibitor L-NMMA (N-G-monomethyl-L-arginine) in 40 patients with CHF due to dilated cardiomyopathy and in 16 normal control subjects. Basal plasma B-type natriuretic peptide (BNP) and nitric oxide concentrations were measured in all subjects. RESULTS Plasma BNP and nitrite/nitrate (NOx) levels in the patients group were significantly greater and baseline FBF was significantly less. Administration of L-NMMA significantly decreased FBF and FVC in both groups. The percent changes in FBF (%FBF) and FVC (%FVC) from the baseline after L-NMMA correlated significantly with plasma BNP level (%FBF: r = 0,72;%FVC: r = 0.76;both p < 0.001). Percent changes in both FBF and FVC were greater in patients with BNP 100 pg/ml than in normal subjects;however, in patients with BNP < 100 pg/ml they were comparable to those in normal subjects. CONCLUSIONS Vasoconstrictive response to L-NMMA in patients with CHF was preserved or enhanced in proportion to the basal plasma BNP level, indicating a close relationship between the contribution of endogenous NO to basal vasomotor tone and the severity of heart failure. (C) 2000 by the American College of Cardiology.

关键词：心钠素/血液酶抑制剂/药理学心力衰竭/血液心力衰竭/病理生理学肌张力/药物作用肌张力/生理学利钠肽脑一氧化氮/生理学局部血流/药物作用局部血流/生理学疾病严重程度指数血管舒缩系统/药物作用血管舒缩系统/病理生理学 ωN-甲基精氨酸/药理学成年人老年人女(雌)性人类男(雄)性中年人

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Contribution of bradykinin receptor dysfunction to abnormal coronary vasomotion in humans

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JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY 2000年第5期36卷 1467-1473页

作者： Prasad, A Husain, S Schenke, W Mincemoyer, R Epstein, N Quyyumi, AA NHLBI NIH Cardiol Branch Bethesda MD 20892 USA

OBJECTIVES The aim of our study was to investigate coronary vascular kinin receptor function in patients with atherosclerosis or its risk factors. BACKGROUND Although acetylcholine (ACH) is used as a probe for testing vascular function in vivo, endogenous bradykinin (BK) regulates resting and flow-mediated epicardial tone. METHODS In 53 patients with mild atherosclerosis or its risk factors and 9 control subjects, endothelium-dependent vasomotion was tested with intracoronary ACH (30 mug/min) and BK (62.5 ng/min and 4 mug/min), and endothelium independent function with sodium nitroprusside. Metabolic vasodilation was assessed during cardiac pacing (n = 19). Correlation with serum angiotensin-converting enzyme (ACE) levels and the ACE insertion/deletion genotype was performed. RESULTS There was progressive impairment in AGH-mediated microvascular dilation with increasing numbers of risk factors (p = 0.025, analysis of variance). By contrast, BK- and sodium nitroprusside-mediated microvascular dilation was similar in all groups. Similarly, there was no correlation between epicardial coronary responses to ACH and BK;segments that constricted or dilated with ACH had similar dilator responses with BK. Bradykinin, but not ACH-mediated vasomotion, was depressed in epicardial segments that constricted with pacing. Finally, epicardial BK responses were depressed in patients with high ACE levels and in those with the ACE DD genotype. CONCLUSIONS Endothelial dysfunction in atherosclerosis appears to be receptor-specific, involving the muscarinic receptor with relative sparing of the kinin receptor pathways. Abnormal reactivity of epicardial coronary arteries during physiologic stress is better represented by BK and not by ACH responses. Bradykinin activity and, hence, physiologic coronary vasomotion appears to be influenced by serum ACE levels and the ACE insertion/deletion genotype. (C) 2000 by the American College of Cardiology.

关键词：乙酰胆碱/药理学腺苷/药理学动脉硬化/病理生理学缓激肽/药理学冠状血管/药物作用冠状血管/病理生理学血流动力学一氧化氮/生理学硝普钠/药理学肽基二肽酶A/血液肽基二肽酶A/遗传学多态现象遗传受体缓激肽/药物作用受体缓激肽/生理学危险因素血管舒缩系统/药物作用血管舒缩系统/病理生理学 ωN-甲基精氨酸/药理学女(雌)性人类男(雄)性中年人

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Relation of preservation of nitric oxide-dependent coronary vasomotor function to plasma vitamin C concentrations in cardiac transplant recipients

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AMERICAN JOURNAL OF CARDIOLOGY 2000年第4期86卷 460-+页

作者： Fang, JC Kinlay, S Hikita, H Suh, JH Piana, RN Selwyn, AP Frei, B Morrow, JD Ganz, P Brigham & Womens Hosp Div Cardiovasc Boston MA 02115 USA Oregon State Univ Linus Pauling Inst Corvallis OR 97331 USA Vanderbilt Univ Dept Med & Pharmacol Nashville TN USA

The contribution of oxidant stress to coronary endothelial dysfunction in cardiac transplant recipients is not known. We found that the plasma vitamin C concentration, but not plasma F-2-isoprostanes, was significantl... 详细信息

关键词：乙酰胆碱/药理学抗氧化剂抗坏血酸/血液抗坏血酸/生理学生物利用度色谱法高压液相冠状血管/药物作用冠状血管/生理学内皮血管/药物作用内皮血管/生理学心脏移植/生理学多元分析一氧化氮/生理学硝酸甘油/药理学手术后期间血管舒张药/药理学血管舒缩系统/药物作用血管舒缩系统/生理学成年人老年人女(雌)性人类男(雄)性中年人

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Arginine vasopressin in the treatment of 50 patients with postcardiotomy vasodilatory shock

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ANNALS OF THORACIC SURGERY 2000年第1期69卷 102-106页

作者： Morales, DLS Gregg, D Helman, DN Williams, MR Naka, Y Landry, DW Oz, MC Columbia Univ Coll Phys & Surg Dept Surg New York NY 10032 USA Columbia Univ Coll Phys & Surg Dept Med New York NY 10032 USA

Background. The barroreflex-mediated secretion of arginine vasopressin has been found to be defective in a variety of vasodilatory shock states, such as postcardiotomy shock, and administration of the hormone markedly improves vasomotor tone and blood pressure. The high incidence of vasodilatory shock in patients undergoing left ventricular assist device (LVAD) implantation makes this population an ideal model in which to assess the risks and benefits of vasopressin. Methods. The medical records of the 102 patients receiving LVADs at Columbia-Presbyterian Medical Center from January 1995 to August 1998 were reviewed. Fifty patients were eligible for study based on a history of arginine vasopressin administration in the operating room or intensive care unit within 24 hours of implantation. Results. Despite LVAD implantation and the administration of vasopressors, patients were hypotensive with a mean arterial pressure less than 60 mm Hg. The administration of vasopressin (0.09 +/- 0.05 U/min) increased mean arterial pressure (58 +/- 13 to 75 +/- 14 mm Hg;p < 0.001) while reducing norepinephrine administration (11.7 +/- 13 to 7.9 +/- 6.0 mcg/min;p = 0.023). There was no significant change in LVAD flow. The incidence of compromised regional perfusion was not different between LVAD patients who received vasopressin as compared to hemodynamically stable LVAD patients who did not receive vasopressin. Conclusions. We have demonstrated vasopressin at low doses to be a safe and an effective vasopressor in 50 patients with postcardiotomy vasodilatory shock. (C) 2000 by The Society of Thoracic Surgeons.

关键词：血管舒张血管舒缩系统/药物作用

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Influence of ageing on vasomotor responses of human epicardial coronary arteries

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PHARMACOLOGY & TOXICOLOGY 2000年第4期86卷 183-191页

作者： Opgaard, OS Ytterberg, HT Saxena, PR Edvinsson, L Erasmus Univ Dept Pharmacol NL-3000 DR Rotterdam Netherlands Univ Hosp Dept Internal Med Lund Sweden

Vasomotor responses to various agonists were studied on isolated circular segments of human epicardial coronary arteries from three different age groups;23-38 pars, 44-58 years and 63-86 years. Noradrenaline had no or only weak contractile effect on coronary arteries from younger patients but induced contraction of all artery segments from older patients. The E-max value was significantly (P<0.0001) higher in arteries from the oldest group compared to each of the two younger age groups, whereas the potency was similar in all three groups. Linear regression analysis of noradrenaline-induced contraction in individual patients revealed a significantly positive age-correlation (correlation coefficient 0.67, P<0.0001). Contraction induced by endothelin-1 and relaxation induced by substance P, calcitonin gene-related peptide and vasoactive intestinal peptide on arteries precontracted with U46619 showed no significant differences in maximum responses and potencies between the three age groups, and no significant linear age-correlation. These data demonstrate a large variability in contractile responses to noradrenaline with contractions seen mostly in coronary arteries from older patients. It thus seems that sympathetic activation could contribute to coronary ischaemia in some patients.

关键词： 15-羟基-11α 9α-(环氧亚甲基)前列腺-5 13-二烯酸/药理学衰老降钙素基因相关肽/药理学心肌疾病/病理生理学冠状血管/药物作用冠状血管/生理学冠状血管/病理生理学剂量效应关系药物内皮缩血管肽类/药理学去甲肾上腺素/药理学 P物质/药理学血管活性肠肽/药理学血管收缩/药物作用血管收缩药/药理学血管舒张/药物作用血管舒缩系统/药物作用血管舒缩系统/生理学血管舒缩系统/病理生理学成年人老年人老年人 80以上人类中年人

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Effect of brimonidine on optic nerve blood flow in rabbits

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AMERICAN JOURNAL OF OPHTHALMOLOGY 1999年第5期128卷 601-605页

作者： Bhandari, A Cioffi, GA Van Buskirk, EM Orgül, S Wang, L Devers Eye Inst Legacy Hlth Syst Portland OR 97210 USA

PURPOSE: Brimonidine is a highly selective alpha(2)-adrenoreceptor agonist that lowers intraocular pressure. The aim of the present study was to analyze in vivo the vasomotor effects and the influence of brimonidine on blood flow within the optic nerve, by means of intraluminal microvascular corrosion casting technique and intravascular injection of colored microspheres. METHODS: New Zealand white rabbits received either brimonidine tartrate 0.2% or placebo (vehicle) topical drops in one eye for 4 weeks. Intraocular pressures were measured at baseline and 4 weeks. The anterior optic nerve microvasculature of four rabbits was examined with corrosion castings for regions of focal vasoconstriction. Optic nerve blood flow was determined in 16 rabbits by means of nonradioactive colored microspheres. RESULTS: The vasoconstriction values of the short posterior ciliary arterial branches in the brimonidine eyes were 16.7% +/- 3.7%. In the fellow untreated eyes, the mean vasoconstriction was 16.6% +/- 2.4%. In the placebo-treated eyes, the average constriction was 15.9% +/- 3.2%;the fellow eyes showed a mean constriction value of 16.1% +/- 5.3%. There was no statistical difference between any of the groups (P = .2). The optic nerve blood flow in the brimonidine-treated rabbits was 0.18 +/- 0.06 ml/mg/min and 0.17 +/- 0.04 ml/mg/min in the treated and the fellow eyes, respectively. The difference between the optic nerve blood flow in the brimonidine-treated eyes and the optic nerve blood flow in all of the untreated eyes (0.19 +/- 0.06 ml/mg/min) also was not statistically different (P = .82). CONCLUSIONS: Long-term application of brimonidine 0.2% does not affect the blood flow or vasomotor activity of the anterior optic nerve. (C) 1999 by Elsevier Science Inc. All rights reserved.

关键词：肾上腺素能α激动剂/药理学睫状体/血液供给腐蚀铸型微循环/药物作用微球体视神经/血液供给喹恶啉类/药理学局部血流/药物作用血管收缩血管舒缩系统/药物作用动物女(雌)性男(雄)性兔

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Improvement of endothelial vasomotor dysfunction by treatment with alpha-tocopherol in patients with high remnant lipoproteins levels

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JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY 1999年第6期33卷 1512-1518页

作者： Kugiyama, K Motoyama, T Doi, H Kawano, H Hirai, N Soejima, H Miyao, Y Takazoe, K Moriyama, Y Mizuno, Y Tsunoda, R Ogawa, H Sakamoto, T Sugiyama, S Yasue, H Kumamoto Univ Sch Med Dept Cardiovasc Med Kumamoto 860 Japan

OBJECTIVES This study sought to examine whether oral intake of alpha-tocopherol, an antioxidant, could improve endothelium-dependent vasorelaxation in patients with high remnant lipoproteins levels. BACKGROUND Remnant lipoproteins are known to be atherogenic and impair endothelium-dependent arterial relaxation, but the underlying mechanisms remain unclear. Oxidative stress is a common feature of various risk factors for atherosclerosis. METHODS Flow-mediated vasodilation of the brachial artery during reactive hyperemia was examined by high resolution ultrasound technique before and at the end of 4 weeks treatment with oral administration of alpha-tocopherol acetate (300 IU/day) or placebo, which was randomly assigned, in 40 patients with high serum levels of remnants and in 30 patients with low remnants levels in the fasting state (>75th percentile and <25th percentile, respectively, of the distribution of remnants levels in 150 consecutive hospitalized patients). RESULTS Before treatment, flow-mediated vasodilation was lower in patients with high remnants levels than in those with low levels (4.1 +/- 0.3% vs. 6.0 +/- 0.5%, p < 0.01). Treatment with alpha-tocopherol but not with placebo significantly increased flow-mediated dilation in patients with high remnants levels (7.5 +/- 0.1% after alpha-tocopherol vs. 4.2 +/- 0.4% after placebo, p < 0.01). in patients with low remnants levels, alpha-tocopherol was not effective. The beneficial effect with alpha-tocopherol in high remnants patients was associated with decrease in plasma levels of thiobarbituric add reactive substances, an indicator of lipid peroxidation (6.6 +/- 0.3 nmol/ml before alpha-tocopherol vs. 4.6 +/- 0.3 after alpha-tocopherol, p < 0.05). CONCLUSIONS Alpha-tocopherol improved impairment of endothelium-dependent vasodilation in patients with high remnants levels. The increase in oxidative stress may at least partly contribute to endorhelial vasomotor dysfunction in patients with high remnants levels.

关键词：抗氧化剂/投药和剂量载脂蛋白类/血液肱动脉/药物作用肱动脉/病理生理学胆固醇/血液冠状动脉疾病/药物疗法冠状动脉疾病/病理生理学内皮血管/药物作用内皮血管/生理学高胆固醇血症/药物疗法高胆固醇血症/病理生理学高甘油三酯血症/药物疗法高甘油三酯血症/病理生理学脂类/血液脂蛋白类/血液血管舒缩系统/药物作用血管舒缩系统/病理生理学维生素E/投药和剂量成年人老年人女(雌)性人类男(雄)性中年人

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Dopaminergic regulation of cerebral cortical microcirculation

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NATURE NEUROSCIENCE 1998年第4期1卷 286-289页

作者： Krimer, LS Muly, EC Williams, GV Goldman-Rakic, PS Yale Univ Sch Med Neurobiol Sect New Haven CT 06510 USA Yale Univ Sch Med Dept Psychiat New Haven CT 06510 USA

Functional variations in cerebral cortical activity are accompanied by local changes in blood flow, but the mechanisms underlying this physiological coupling are not well understood. Here we report that dopamine, a neurotransmitter normally associated with neuromodulatory actions, may directly affect local cortical blood flow. Using light and electron-microscopic immunocytochemistry, we show that dopaminergic axons innervate the intraparenchymal microvessels. We also provide evidence in an in vitro slice preparation that dopamine produces vasomotor responses in the cortical vasculature. These anatomical and physiological observations reveal a previously unknown source of regulation of the microvasculature by dopamine. The findings may be relevant to the mechanisms underlying changes in blood flow observed in circulatory and neuropsychiatric disorders.

关键词：轴突/生理学血管/药物作用血管/神经支配大脑皮质/血液供给多巴胺/药理学多巴胺/生理学免疫组织化学恒河猴微循环/药物作用微循环/生理学显微镜检查电子神经末梢/代谢神经末梢/超微结构血管舒缩系统/药物作用动物

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EFFECTS OF HEXAMETHONIUM, BIPERIDEN AND PHENTOLAMINE ON VASOCONSTRICTIVE EFFECTS OF OCULOMOTOR NERVE-STIMULATION IN RABBITS

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EXPERIMENTAL EYE RESEARCH 1976年第6期23卷 615-622页

作者： BILL, A STJERNSCHANTZ, J ALM, A UNIV UPPSALA CTR BIOMED INST PHYSIOL & MED BIOPHYS UPPSALA SWEDEN

In rabbits intracranial stimulation of the oculomotor nerve causes vasoconstriction in the anterior uvea and vasodilation in the choroid and an attempt was made to analyze the mechanism involved in the vasoconstrictive response to stimulation. The oculomotor nerve was stimulated unilaterally, and regional blood flow was determined in both eyes using radioactively labeled microspheres. Hexamethonium bromide, in a dose of 40-80 mg/kg body weight, completely abolished the vasoconstrictive response in the iris and the ciliary processes. The blood flow in all parts of the uvea tended to be higher on the stimulated side than on the control side. The parasympatholytic agent biperiden lactate, in a dose of 2.5-5 mg/kg body wt, reduced the response in the iris, but no significant change was observed in the ciliary processes. The .alpha.-adrenergic blocking agent phentolamine chloride, in a dose of 10-15 mg/kg body wt had no significant effect on the response in the iris but reversed the effect in the ciliary processes. A combination of biperiden and phentolamine totally abolished the vasoconstrictive response in the iris, and there was increased blood flow in the ciliary processes on the stimulated side. Intracranial stimulation of the oculomotor nerve and possibly of adjacent structures apparently caused a release of vasodilating and vasoconstricting agents in the uvea. The vasoconstrictive effect was partly muscarinic, possibly due to miosis, and partly due to stimulation of receptors sensitive to phentolamine. A ganglion or ganglion-like receptors, somewhere between the site of stimulation and the effector cells, seem to be involved in the transmission of the vasoconstrictive impulses.

关键词：比哌立登/药理学脉络膜/血液供给六甲胺化合物/药理学动眼神经/生理学酚妥拉明/药理学哌啶类/药理学葡萄膜/血液供给血管舒缩系统/药物作用血管舒缩系统/生理学动物女(雌)性男(雄)性兔

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ACTIVATION OF ANAEROBIC METABOLISM IN CAT SKELETAL-MUSCLE DURING CHOLINERGIC SYMPATHETIC VASODILATATION

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PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY 1976年第1期367卷 37-42页

作者： BERDINA, NA RODIONOV, IM MOSCOW STATE UNIV BIOL & PEDOL FAC ANIM PHYSIOL DEPT MOSCOW USSR

Phosphorylase activity was increased 2-fold as compared with the control value (79% and 39%, respectively) within the first 2-3 s of the vasomotor effect elicited in the skeletal muscle by sympathetic stimulation. Phosphorylase activity was still high during the period of maximum blood flow, although to a lesser extent (54% and 45%). During the restoration phase of the initial rate of blood flow the values of phosphorylase activity were the same in the experimental and control sample. AMP content did not increase with initiation of the vasomotor effect, suggesting that the increase in phosphorylase activity is due to an increase in phosphorylase a rather than to the activation of phosphorylase b by AMP. Atropine blocks both the dilator effect and phosphorylase activation elicited by sympathetic stimulation. Acetylcholine, injected intraarterially or added to a muscle homogenate, increases phosphorylase activity. Acetylcholine, released by sympathetic nerve endings, probably performs a 2nd mediator function, that of activating anaerobic metabolism in the skeletal muscle. The 2 mediator functions of acetylcholine seem spatially delimited.

关键词：乙酰胆碱/药理学腺苷一磷酸/代谢厌氧生活阿托品/药理学二氢麦角毒碱/药理学肌/血液供给肌/代谢副交感神经系统/生理学磷酸化酶类/代谢普萘洛尔/药理学血管舒缩系统/药物作用血管舒缩系统/生理学动物猫

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