• Refine Query
  • Source
  • Publication year
  • to
  • Language
  • 13
  • 8
  • 3
  • Tagged with
  • 28
  • 8
  • 6
  • 6
  • 5
  • 5
  • 5
  • 4
  • 4
  • 3
  • 3
  • 3
  • 3
  • 3
  • 2
  • About
  • The Global ETD Search service is a free service for researchers to find electronic theses and dissertations. This service is provided by the Networked Digital Library of Theses and Dissertations.
    Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
11

Vasodilators and venous tone

D'Oyley, Heather M. January 1988 (has links)
The objective of these experiments was to investigate the effects of various membrane receptor-mediated and receptor-independent vasodilators on the resistance and capacitance vessels of conscious, unrestrained rats by measuring mean arterial pressure (MAP) and mean circulatory filling pressure (MCFP), an index of total body venous tone. ln the first set of experiments the dose-response effects of the directly-acting vasodilators nitroglycerin, sodium nitroprusside and hydralazine were determined in intact rats as well as in rats treated with the ganglionic blocker, hexamethonium. The effects of these drugs were compared with those of the vehicle, normal saline, in control rats. In intact rats, iv infusion of nitroglycerin did not alter MAP while iv infusions of nitroprusside and hydralazine caused dose-dependent decreases in MAP. In intact rats, nitroglycerin and sodium nitroprusside did. not affect MCFP while hydralazine increased MCFP. After treatment with hexamethonium all three drugs decreased MCFP, though the decreases in MCFP caused by hydralazine were not significantly different from the corresponding changes in saline-treated rats. Therefore, sodium nitroprusside and hydralazine but not nitroglycerin were effective arteriolar dilators in intact rats; all three drugs dilated arterioles in ganglionic-blocked rats, ln intact rats, the direct venodilator actions of nitroprusside and nitroglycerin were masked by endogenous sympathetic tone. When sympathetic nerve activity was attenuated, both drugs had venodilatory effects. Hydralazine, on the other hand, hao insignificant venodilatory effects both in the presence and absence of the sympathetic reflexes. In the second set of experiments we determined the dose-response effects of hexamethonium, phentolamine, prazosin and rauwolscine — the latter being non-selective ⍺, ⍺₁-selective, and ⍺₂-selective adrenoceptor antagonists, respectively — in intact rats. Prazosin and rauwolscine were also administered to rats with reflexly increased venous tone induced by the infusion of hydralazine. In intact rats iv infusions of prazosin, phentolamine and rauwolscine all caused dose-dependent decreases in MAP; only rauwolscine reduced MCFP to levels slightly below control. Hexamethonium caused a aecrease in MAP as well as a markea reduction in MCFP. After venous tone was raised by the infusion of hydralazine, both prazosin and rauwolscine dose-dependently decreased MCFP. Therefore, the resistance and capacitance vessels contain both ⍺₁- and ⍺₂-adrenoceptors. in the intact rat, however, the capacitance vessels are somewhat resistant to the effects of postjunctionally acting ⍺-antagonists in contrast to the effects of hexamethonium which acts at the level of the ganglion. / Medicine, Faculty of / Anesthesiology, Pharmacology and Therapeutics, Department of / Graduate
12

Modulation of intracellular calcium by vasoconstrictors and vasodilators in the rat aorta /

Heaslip, Richard Joseph January 1982 (has links)
No description available.
13

A study on vanilloid receptor agonists on blood flow and plasma extravasation in the rat knee joint.

January 2004 (has links)
Luk Wing Sze, Phoebe. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2004. / Includes bibliographical references (leaves 173-190). / Abstracts in English and Chinese. / Abstract --- p.I / Acknowledgement --- p.XII / Publications Based on the Work in this Thesis --- p.XIII / Abbreviations --- p.IX / Table of Contents --- p.X / Chapter Chapter 1 --- Introduction --- p.1 / Chapter 1.1. --- Arthritis and Inflammation --- p.1 / Chapter 1.1.1. --- Tissue Reaction in Inflammation --- p.2 / Chapter 1.1.1.1. --- Mechanism of Vasodilatation --- p.2 / Chapter 1.1.1.2. --- Plasma Extravasation --- p.5 / Chapter 1.2. --- Neurogenic Inflammation --- p.8 / Chapter 1.2.1. --- Axon Reflex and Local Efferent Action of Primary Afferents --- p.9 / Chapter 1.2.2. --- Mediators of Neurogenic Inflammation --- p.10 / Chapter 1.2.3. --- Microvascular Effect of Substance P --- p.11 / Chapter 1.2.4. --- Microvascular Effect of Calcitonin Gene-Related Peptide --- p.13 / Chapter 1.3. --- Neurogenic Inflammation in the Joint --- p.16 / Chapter 1.3.1. --- Neuropeptides in Arthritic Knee --- p.16 / Chapter 1.3.2. --- Effects of Neuropeptides on Normal Knee --- p.16 / Chapter 1.3.3. --- Effects of Neuropeptides on Inflamed Knee --- p.17 / Chapter 1.3.4. --- Activation of Efferent Function of the Nerves --- p.19 / Chapter 1.4. --- Vanilloid Receptor --- p.20 / Chapter 1.4.1. --- The Use of Capsaicin as an Experimental Tool --- p.20 / Chapter 1.4.2. --- Identification of Vanilloid Receptor --- p.21 / Chapter 1.4.3. --- Molecular Biology of Vanilloid Receptor --- p.22 / Chapter 1.4.4. --- Electrophysiolgocial Properties of Vanilloid Receptors --- p.23 / Chapter 1.5. --- Activation of Vanilloid Receptors - A Detector of Physical Stimuli --- p.23 / Chapter 1.5.1. --- Exogenous Activators of Vanilloid Receptors --- p.25 / Chapter 1.5.2. --- Endogenous Activators of Vanilloid Receptors --- p.26 / Chapter 1.5.2.1. --- Anandamide as an Endovanilloid --- p.26 / Chapter 1.5.2.2. --- Other Possible Endovanilloid --- p.28 / Chapter 1.5.3. --- Biological Effects of Capsaicin --- p.29 / Chapter 1.5.3.1. --- Efferent Function: Neuropeptide Release --- p.29 / Chapter 1.5.3.2. --- Desensitization --- p.30 / Chapter 1.5.3.3. --- Neurotoxicity --- p.32 / Chapter 1.5.4. --- Biological Effects of Anandamide --- p.33 / Chapter 1.5.4.1. --- Vascular Effect of Anandamide --- p.33 / Chapter 1.5.4.2. --- Interaction of the Vanilloid and Cannabinoid System --- p.38 / Chapter 1.6. --- Aim of Study --- p.39 / Chapter Chapter 2 --- Methods --- p.40 / Chapter 2.1. --- Materials --- p.40 / Chapter 2.2. --- Protocols --- p.42 / Chapter 2.2.1. --- General Procedures --- p.42 / Chapter 2.2.2. --- Preparatory Procedure --- p.43 / Chapter 2.3. --- Measurement of Knee Joint Blood Flow --- p.46 / Chapter 2.3.1. --- Animal Preparation for Measuring Knee Joint Blood Flow --- p.48 / Chapter 2.3.2. --- Specific Procedures --- p.49 / Chapter 2.3.3. --- Image Analysis --- p.51 / Chapter 2.3.4. --- Data Analysis --- p.52 / Chapter 2.4. --- Quantification of Plasma Protein Extravasation --- p.52 / Chapter 2.4.1. --- Experimental Procedure --- p.53 / Chapter 2.4.2. --- Measurement of Evans Blue Content --- p.53 / Chapter 2.4.3. --- Measurement of Knee Joint Size --- p.54 / Chapter 2.5. --- Effect of Capsaicin on Acute Joint Inflammation --- p.54 / Chapter Chapter 3 --- Results --- p.55 / Chapter 3.1. --- Vanilloids on Knee Joint Blood Flow --- p.55 / Chapter 3.1.1. --- Capsaicin --- p.55 / Chapter 3.1.1.1. --- Cumulative Dosing of Capsaicin --- p.55 / Chapter 3.1.1.2. --- Time Course of Capsaicin-induced Vasodilatation --- p.55 / Chapter 3.1.1.3. --- VR1 Antagonists on Capsaicin-induced Vasodilatation --- p.57 / Chapter 3.1.1.4. --- NK1 Antagonists on Capsaicin-induced Vasodilatation --- p.58 / Chapter 3.1.1.5. --- CGRP Antagonist on Capsaicin-induced Vasodilatation --- p.60 / Chapter 3.1.1.6. --- Denervation on Capsaicin-induced Vasodilatation --- p.61 / Chapter 3.1.2. --- Anandamide --- p.62 / Chapter 3.1.2.1. --- Dose Responses of Anandamide --- p.62 / Chapter 3.1.2.2. --- Time Course of Anandamide-induced Vasodilatation --- p.63 / Chapter 3.1.2.3. --- VR1 Antagonist on Anandamide-induced Vasodilatation --- p.64 / Chapter 3.1.2.4. --- NK1 Receptor Antagonists on Anandamide-induced Vasodilatation --- p.65 / Chapter 3.1.2.5. --- CGRP Receptor Antagonist on Anandamide-induced Vasodilatation --- p.67 / Chapter 3.1.2.6. --- CB1 Receptor Antagonist on Anandamide-induced Vasodilatation --- p.67 / Chapter 3.1.2.7. --- CB2 Receptor Antagonist on Anandamide-induced Vasodilatation --- p.68 / Chapter 3.1.2.8. --- Anandamide Transporter Inhibitor on Anandamide-induced Vasodilatation --- p.69 / Chapter 3.1.2.9. --- Effects of Denervation on Anandamide-induced Vasodilatation --- p.70 / Chapter 3.2. --- Vanilloids on Plasma Extravasation --- p.71 / Chapter 3.2.1. --- Saline injection on Plasma Extravasation --- p.71 / Chapter 3.2.2. --- Capsaicin on Plasma Extravasation --- p.72 / Chapter 3.2.3. --- Capsaicin on Knee Joint Sizes --- p.73 / Chapter 3.2.4. --- Anandamide on Plasma Extravasation --- p.73 / Chapter 3.2.5. --- Anandamide on Knee Joint Size --- p.73 / Chapter 3.3. --- Effects of Vanilloid Agonists on Carrageenan-induced Acute Inflammation --- p.74 / Chapter 3.3.1. --- Capsaicin on Carrageenan-induced Plasma Extravasation --- p.74 / Chapter 3.3.2. --- Capsaicin on Carrageenan-induced Joint Swelling --- p.77 / Chapter 3.3.3. --- Anandamide on Carrageenan-induced Plasma Extravasation --- p.79 / Chapter 3.3.4. --- Anandamide on Carrageenan-induced Joint Swelling --- p.80 / Chapter Chapter 4 --- Discussion --- p.150 / Chapter 4.1. --- Capsaicin-induced Long Lasting Vasodilatation --- p.151 / Chapter 4.2. --- Capsaicin-induced Vasodilatation 一 a VR1 Mediated Effect? --- p.153 / Chapter 4.3. --- Substance P and CGRP in Capsaicin-induced Vasodilatation --- p.155 / Chapter 4.4. --- Anandamide-induced Vasodilatation --- p.157 / Chapter 4.5. --- VR1 in AEA-induced Vasodilatation --- p.159 / Chapter 4.6. --- Neuropeptides in AEA-induced Vasodilatation --- p.160 / Chapter 4.7. --- Cannabinoid Receptors in AEA-induced Vasodilatation --- p.161 / Chapter 4.8. --- Role of Anandamide Transporter in AEA-induced Vasodilatation --- p.163 / Chapter 4.9. --- A Neural Mechanism for Capsaicin- and AEA-induced Vasodilatation? --- p.164 / Chapter 4.10. --- Effects of Capsaicin and AEA on Plasma Extravasation --- p.167 / Chapter 4.11. --- Capsaicin and Anandamide in Acute Inflammation --- p.169 / Chapter 4.12. --- Conclusion --- p.170 / References --- p.173
14

TRPV4-TRPC1-KCa1.1 complex: its function in vascular tone regulation.

January 2014 (has links)
一氧化氮(NO)和內皮源性超極化因子(EDHFs)是內皮衍生的血管舒張因子兩大類。 EETs是構成EDHFs的主要類型,這是由花生四烯酸通過細胞色素P450 (CYP)表氧化酶的催化活性得到。雖然這兩個EET和NO誘導血管舒張,從而降低血壓,許多報告表明,NO對EET引起的血管舒張起抑製作用。然而,不管它的重要性,有關一氧化氮對EETs的抑制作用的機理尚未完全了解。 / 在本研究中,我調查了一氧化氮對EET的負調控。通過膜電位和動脈張力測量,我們發現, 11,12-EET可引起內皮剝脫豬冠狀動脈平滑肌細胞膜超極化和血管舒張。該反應被S-亞硝基-N-乙酰青黴胺(SNAP)和8-Br-cGMP,一個NO的供體和cGMP的膜穿透物類似物,分別抑制。 SNAP和8-Br-cGMP對11,12-EET引起的細胞膜超極化和血管舒張的抑製作用被羥鈷胺,一氧化氮清除劑; ODQ ,鳥苷酸環化酶抑製劑;和KT5823 ,蛋白激酶G(PKG)抑製劑逆轉。 SNAP和8-Br-cGMP對EET反應的抑製作用也被過度供應外源性激酶底物, TAT-TRPC1S¹⁷²和TAT -TRPC1T³¹³廢除。羥鈷胺,ODQ, KT5823, TAT -TRPC1,和TAT -scrambled獨自使用不影響11,12-EET引起的細胞膜超極化和血管舒張作用。然而,獨自使用14,15-EEZE(EET的拮抗劑)抑制了11,12-EET的作用。 此外,磷酸化試驗表明, PKG可以直接在Ser172和Thr313位點磷酸化TRPC1 。此外,TRPV4 , TRPC1 ,或KCa1.1被選擇性地抑制時,11,12-EET未能引起細胞膜超極化和血管舒張。免疫共沉澱研究表明, TRPV4 , TRPC1和KCa1.1物理上彼此相關聯。 / 以上結果表明,NO-cGMP-PKG通路可通過TRPC1的磷酸化來抑制11,12- EETs在冠狀動脈血管平滑肌細胞上的作用。此外,TRPV4,TRPC1和KCa1.1參與11,12-EET誘導平滑肌超極化和血管舒張,他們可能互相關聯。從本研究的結果表明,NO和cGMP可通過PKG-介導的TRPC1的磷酸化,抑製EET誘導的平滑肌超極化和血管舒張。 / Nitric oxide (NO) and endothelium-derived hyperpolarizing factors (EDHFs) are two main classes of endothelium-derived vascular relaxant factors. EETs constitute a major type of EDHFs, which are derived from arachidonic acids via the catalytic activity of cytochrome P450 (CYP) epoxygenases. Although both EET and NO induce vascular relaxation, thus reduce blood pressure, numerous reports demonstrated that NO exerts an inhibitory action on EET-induced vascular relaxation. However, despite of its importance, the mechanisms related to the inhibitory effects of NO on EETs are incompletely understood. / In the present study, I investigated the scheme for negative regulation of NO on EET action. Through measurements of membrane potential and arterial tension, we showed that 11,12-EET could induce membrane hyperpolarization and vascular relaxation in endothelium-denuded porcine coronary arteries. The responses were suppressed by S-nitroso-N-acetylpenicillamine (SNAP) and 8-Br-cGMP, a NO donor and a membrane-permeant analogue of cGMP, respectively. The inhibitory actions of SNAP and 8-Br-cGMP on 11,12-EET-induced membrane hyperpolarization and vascular relaxation were reversed by hydroxocobalamin, a NO scavenger; ODQ, a guanylyl cyclase inhibitor; and KT5823, a protein kinase G (PKG) inhibitor. The inhibitory actions of SNAP and 8-Br-cGMP on EET responses were also abrogated by shielding TRPC1-PKG phosphorylation sites with excessive supply of exogenous PKG substrates, TAT-TRPC1S¹⁷² and TAT-TRPC1T³¹³. Hydroxocobalamin, ODQ, KT5823, TAT-TRPC1 and TAT-scrambled alone has no effect on 11,12-EET-induced membrane hyperpolarization and vascular relaxation. However, 14,15-EEZE (a selective EET antagonist) alone inhibits the action of 11,12-EET. Furthermore, phosphorylation assay was performed and it demonstrated that PKG could directly phosphorylate TRPC1 at Ser¹⁷² and Thr³¹³. In addition, 11,12-EET failed to induce membrane hyperpolarization and vascular relaxation when TRPV4, TRPC1, or KCa1.1 was selectively inhibited. Co-immunoprecipitation studies demonstrated that TRPV4, TRPC1 and KCa1.1 physically associated with each other in smooth muscle cells. / Taking together, our findings demonstrated that the NO-cGMP-PKG pathway may act through the phosphorylation of TRPC1 to inhibit the action of 11,12-EETs in coronary arterial smooth muscle cells. Furthermore, TRPV4, TRPC1 and KCa1.1 are critically involved in the 11,12-EET-induced smooth muscle hyperpolarization and relaxation and that they may physically associate with each other. The results from this study demonstrated that NO and cGMP could lead to PKG-mediated phosphorylation of TRPC1, resulting in an inhibition of EET-induced smooth muscle hyperpolarization and vascular relaxation. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Zhang, Peng. / "Ca" on title page is subscript. / Thesis (Ph.D.) Chinese University of Hong Kong, 2014. / Includes bibliographical references (leaves 115-133). / Abstracts also in Chinese.
15

Avaliação cardíaca de cães com degeneração valvar mixomatosa durante o emprego de enalapril, losartana, furosemida e suas combinações

Gómez Ortiz, Edna Mireya [UNESP] 22 February 2011 (has links) (PDF)
Made available in DSpace on 2014-06-11T19:23:46Z (GMT). No. of bitstreams: 0 Previous issue date: 2011-02-22Bitstream added on 2014-06-13T20:11:36Z : No. of bitstreams: 1 gomezortiz_em_me_jabo.pdf: 655486 bytes, checksum: c6735fb13135ba2645745a2e60a3ec5e (MD5) / Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) / A degeneração valvar mixomatosa (DVM) é a afecção cardíaca mais comum em cães. O tratamento da insuficiência cardíaca congestiva (ICC) decorrente da DVM baseia-se no uso de inibidores da enzima conversora de angiotensina - ECA. Antagonistas dos receptores de angiotensina II - ARAs promovem o bloqueio completo da angiotensina II, e são usados no tratamento de ICC em humanos, mas não é comum em cães. O objetivo desta pesquisa foi comparar as respostas clínicas de cães com DVM tratados com enalapril- ECA, losartana -ARAs, furosemida – diurético de alça ou suas combinações. Vinte e nove cães foram distribuídos em cinco grupos dependendo da classe de ICC (Ib ou II) e do tratamento: G1 - Ib, enalapril; G2 – Ib, losartana; G3 – II, enalapril + furosemida; G4 – II, losartana + furosemida; G5- II, enalapril + losartana. Realizou-se exame físico, e determinaramse medidas eletrocardiográficas e pressão arterial nos dias 0, 14, 28 e 56 após início dos tratamentos. Medida radiográfica - Vertebral Heart Size, e variáveis ecodopplercardiográficas obtiveram-se nos dias 0 e 56. Submeteram-se os dados a analise de variância com medidas repetidas. Não houve diferenças (P>0,05) nas variáveis ecodopplercardiográficas, eletrocardiográficas e radiográficas quando comparados cães tratados com enalapril, losartana e suas combinações, tanto com ICC da classe Ib quanto da II. Nos cães de todos os grupos houve diminuição (P> 0,05), a través do tempo, da Vertebral Heart Size e redução (P> 0,05) da duração da onda P e do complexo QRS. Concluiu-se que losartana atua de forma similar ao enalapril no tratamento inicial (primeiros 56 dias) de cães com DVM em fases Ib e II da ICC / Degenerative myxomatous mitral valve disease (DMMVD) is the most common cardiac disease in dogs. The treatment of congestive heart failure (CHF) due to DMMVD is based, among others, on the use of vasodilators, like angiotensin converting enzyme (ACE) inhibitors. Recently, other vasodilators such as angiotensin II receptor antagonists (ARAs) have been used in humans with CHF and have promoted a complete blockage of angiotensin II, but is not common in dogs. Thus, the purpose of this investigation was to compare clinical outcomes of enalapril- ACA , losartan - ARAs, furosemide loop diuretic and its combinations in the treatment of CHF in dogs with DMMVD. For this, 29 dogs were distributed into five groups regardless of class of CHF (Ib or II) and treatment: G1- Ib, enalapril; G2 – Ib losartan; G3 enlapril + furosemida; G4 losartan + furosemida; G5 enalapril + losartan. Physical examination, electrocardiographic examinations and determination of blood pressure were performed on day 0, 14, 28 and 56 after the begging of treatment, whereas radiographic and echocardiogram just at the day 0 and 56. Data was submitted to analysis of variance with repeated measures. there was no difference (P> 0.05) when comparing the dogs treated with enalapril and losartan and its combinations within the classes Ib and II for echoDopplercardiographic, electrocardiographic and radiographic parameters. The measuring radiographic Vertebral Heart Size was significant (P <0.05) decreased this variable to the time factor, of all groups and the P-wave and the QRS complex duration (P <0.05). It was concluded that losartan has a similar effect of enalapril in the initial treatment (first 56 days) in dogs with DMMVD class Ib and II of the CHF
16

Avaliação cardíaca de cães com degeneração valvar mixomatosa durante o emprego de enalapril, losartana, furosemida e suas combinações /

Gomez Ortiz, Edna Mireya. January 2011 (has links)
Orientador: Aparecido Antonio Camacho / Banca: Mirela Tinucci Costa / Banca: Wagner Luis Ferreira / Resumo: A degeneração valvar mixomatosa (DVM) é a afecção cardíaca mais comum em cães. O tratamento da insuficiência cardíaca congestiva (ICC) decorrente da DVM baseia-se no uso de inibidores da enzima conversora de angiotensina - ECA. Antagonistas dos receptores de angiotensina II - ARAs promovem o bloqueio completo da angiotensina II, e são usados no tratamento de ICC em humanos, mas não é comum em cães. O objetivo desta pesquisa foi comparar as respostas clínicas de cães com DVM tratados com enalapril- ECA, losartana -ARAs, furosemida - diurético de alça ou suas combinações. Vinte e nove cães foram distribuídos em cinco grupos dependendo da classe de ICC (Ib ou II) e do tratamento: G1 - Ib, enalapril; G2 - Ib, losartana; G3 - II, enalapril + furosemida; G4 - II, losartana + furosemida; G5- II, enalapril + losartana. Realizou-se exame físico, e determinaramse medidas eletrocardiográficas e pressão arterial nos dias 0, 14, 28 e 56 após início dos tratamentos. Medida radiográfica - Vertebral Heart Size, e variáveis ecodopplercardiográficas obtiveram-se nos dias 0 e 56. Submeteram-se os dados a analise de variância com medidas repetidas. Não houve diferenças (P>0,05) nas variáveis ecodopplercardiográficas, eletrocardiográficas e radiográficas quando comparados cães tratados com enalapril, losartana e suas combinações, tanto com ICC da classe Ib quanto da II. Nos cães de todos os grupos houve diminuição (P> 0,05), a través do tempo, da Vertebral Heart Size e redução (P> 0,05) da duração da onda P e do complexo QRS. Concluiu-se que losartana atua de forma similar ao enalapril no tratamento inicial (primeiros 56 dias) de cães com DVM em fases Ib e II da ICC / Abstract: Degenerative myxomatous mitral valve disease (DMMVD) is the most common cardiac disease in dogs. The treatment of congestive heart failure (CHF) due to DMMVD is based, among others, on the use of vasodilators, like angiotensin converting enzyme (ACE) inhibitors. Recently, other vasodilators such as angiotensin II receptor antagonists (ARAs) have been used in humans with CHF and have promoted a complete blockage of angiotensin II, but is not common in dogs. Thus, the purpose of this investigation was to compare clinical outcomes of enalapril- ACA , losartan - ARAs, furosemide loop diuretic and its combinations in the treatment of CHF in dogs with DMMVD. For this, 29 dogs were distributed into five groups regardless of class of CHF (Ib or II) and treatment: G1- Ib, enalapril; G2 - Ib losartan; G3 enlapril + furosemida; G4 losartan + furosemida; G5 enalapril + losartan. Physical examination, electrocardiographic examinations and determination of blood pressure were performed on day 0, 14, 28 and 56 after the begging of treatment, whereas radiographic and echocardiogram just at the day 0 and 56. Data was submitted to analysis of variance with repeated measures. there was no difference (P> 0.05) when comparing the dogs treated with enalapril and losartan and its combinations within the classes Ib and II for echoDopplercardiographic, electrocardiographic and radiographic parameters. The measuring radiographic Vertebral Heart Size was significant (P <0.05) decreased this variable to the time factor, of all groups and the P-wave and the QRS complex duration (P <0.05). It was concluded that losartan has a similar effect of enalapril in the initial treatment (first 56 days) in dogs with DMMVD class Ib and II of the CHF / Mestre
17

The central and peripheral hemodynamic effects of vasodilator therapy in a dog model of heart failure /

Forcino, Carroll Douglas January 1984 (has links)
No description available.
18

N-hydroxyguanidines and related compounds as nitric oxide donors

Kulczynska, Agnieszka January 2009 (has links)
The design of new, improved NO-donor drugs is an important pharmacological objective due to the biological importance of nitric oxide. N-Hydroxyguanidines represent a useful class of NO donors where the mechanism of action is based on the biosynthetic pathway for NO. Thirty new N-arylalkyl-N’-hydroxyguanidines were synthesized and their vasodilatation activity examined by myography in rat aortic rings. The observed relaxations were reversed by ODQ, which is an inhibitor of the guanylate cyclase, implying that this was an NO dependent vasodilatation. The most active compounds were also tested in the isolated perfused kidney (IPK) giving the vasodilatation properties. Preliminary results indicated that N-phenyl-N’- hydroxyguanidine showed the best pharmacological profile with EC₅₀= 19.9 μM and ca. 100% reversibility with ODQ. A series of N-phenylalkyl-N’-hydroxyguanidines were synthesised. NO donor activity was found to be fairly constant up to three methylene groups, and then decreased. Substitutions in the benzene ring of N-phenylethyl-N’-hydroxyguanidine demonstrated that various electron-withdrawing and electron-donating groups in the para position did not significantly affect the NO donor activity of this series of analogues. The nitro and trifluoromethyl substituted compounds gave the best biological profiles. Additionally, a novel heterocyclic, N–furfuryl-N’–hydroxyguanidine possessed very promising vasodilatation properties. In general, almost all the N-arylalkyl-N’-hydroxyguanidines behaved as potent NO donors in the rat aorta assay. In order to establish the influence of the free NH₂ group in the hydroxyguanidine functionality on the vasodilatation properties, N,N-dimethyl and N-methyl-N’- hydroxyguanidines were successfully synthesised. Unfortunately, they have not been tested yet in the biological assay. However, their NMR spectra showed some unusual features and their detailed analysis and X-ray data are presented herein. In addition a series of hydroxamic acids was synthesised and the NO donor activity investigated using the same biological methodology. It was found that the 3-phenylpropionohydroxamic acid was the most potent compound with EC₅₀ = 6 μM and ODQ = 96%. However, behavior in the IPK indicated that hydroxamic acids did not undergo the same biological pathway as in the rat aorta. Two different types of enzyme-activated pro-drugs were designed using N-hydroxyguanidines as the NO donating molecule. Synthetic studies towards these targets were carried out using various synthetic approaches. The desired molecules have not yet been synthesised but the chemistry explored so far has indicated potentially more successful approaches that could be attempted.
19

Effects of hindlimb unweighting on soleus muscle resistance artery endothelial function and eNOS expression

Schrage, William January 2001 (has links)
Thesis (Ph. D.)--University of Missouri--Columbia, 2001. / Typescript. Vita. Includes bibliographical references (leaves 141-150). Also available on the Internet.
20

Interferência de vasodilatadores na hidrólise de nucleotídeos da adenina em plaquetas de pacientes hipertensos / Interference of vasodilators in the hydrolysis of adenine nucleotide on platelets of hypertensive patients

Lunkes, Daniéle Sausen 19 January 2009 (has links)
The thrombogenic process that affects the hypertensive patient is associated with regulatory mechanisms present in the vascular endothelium. These mechanisms involve the release of a endothelium-derived relaxing factor, ectonucleotidases and calcium ions. Considering that vasodilators act both on blood pressure and on homeostasis, we evaluated the interference of different vasodilators on platelet NTPDase activity in hypertensive and healthy patients, with the objective of verifying patient sensitivity to vasodilators. In addition, the kinetic behavior of NTPDase was determined in the presence of the vasodilator that showed the greatest inhibitory influence. The results showed a decrease in NTPDase activity in the presence of arginine (0.025 mM 3.0 mM), sodium nitroprusside (0.01 mM 2.0 mM) and hydralazine (20.0 μM 90.0 μM), when tested for ATP and ADP substrate. However, the hydrolysis of ATP and ADP substrates increased when tested in the presence of arginine in the control group. No effects on enzyme activities were observed when pharmacological doses of captopril were tested in vitro. Kinetic behavior studies were estimated in the presence of sodium nitroprusside, which caused a mixed inhibition. The Km values increased and Vmax decreased with increasing sodium nitroprusside concentrations. The IC50 values were 3.66 mM and 2.64 mM (control group) and 2.08 mM and 3.15 mM (hypertensive group) for ATP and ADP, respectively. The Ki values obtained were 0.345 mM and 2.00 mM for the control group and 0.167mM and 0.325 mM for the hypertensive group, using ATP and ADP as substrate, respectively. In conclusion, based on these results it is possible to speculate that there is an interaction between vasodilators, donors of nitric oxide, and the inhibition of adenine nucleotide hydrolysis on platelets of hipertensive patients. / O processo trombogênico que afeta os pacientes hipertensos está associado com mecanismos regulatórios presentes no endotélio vascular. Esses mecanismos envolvem o fator de relaxamento do endotélio, as ectonucleotidases e íons cálcio. Considerando que os vasodilatadores atuam em ambos, na pressão sangüínea e na homeostase, foi avaliada a interferência de diferentes vasodilatadores na atividade da NTPDase de plaquetas de hipertensos e pacientes saudáveis, com o objetivo de verificar a sensibilidade destes pacientes aos vasodilatadores. Além disso, foi determinado o comportamento cinético da NTPDase na presença do vasodilatador que apresentou maior influência inibitória. Os resultados mostraram uma diminuição na atividade da NTPDase na presença de arginina (0,025 mM 3.0 mM), nitroprussiato de sódio (0,01 2,0 mM) e hidralazina (20,0 μM 90,0 μM), quando testada para os substratos ATP e ADP em plaquetas do grupo hipertensos. Porém, a hidrólise dos substratos ATP e ADP aumentou quando testado na presença de arginina no grupo controle. Nenhum efeito foi observado sobre a atividade da enzima quando doses farmacológicas de captopril foram testadas in vitro. Estudos do comportamento cinético foram realizados na presença de nitroprussiato de sódio, o qual causou uma inibição mista. Os valores de Km aumentaram e os de Vmax diminuíram com o aumento da concentração de nitroprussiato de sódio. Os valores de IC50 foram 3,66 mM e 2,64 mM (grupo controle) e 2,08 mM e 3,15 mM (grupo hipertenso) para ATP e ADP, respectivamente. Os valores de Ki obtidos foram 0,167 mM e 0,325 mM para o grupo hipertensos, usando ATP e ADP como substrato, respectivamente. Contudo, baseado nos resultados encontrados, é possível sugerir que existe uma interação entre vasodilatadores, doadores de óxido nítrico e a inibição da hidrólise de nucleotídeos da adenina em plaquetas de pacientes hipertensos.

Page generated in 0.0451 seconds