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Front Matter |
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Abstract
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Abstract
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Studies in Isolated Organs |
Michael Gralinski,Liomar A. A. Neves,Olga Tiniakova |
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Abstract
Angus and Wright (2000) described in detail various techniques to study the pharmacodynamics of isolated large and small blood vessels.
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Cardiovascular Analysis In Vivo |
Michael Gralinski,Liomar A. A. Neves,Olga Tiniakova |
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Abstract
The test is used to detect the effect of compounds on blood pressure and heart rate of anesthetized rats and to check for possible interference with adrenergic receptors. Antihypertensive agents with different mechanisms of action can be detected with this test.
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Methods to Induce Experimental Hypertension |
Michael Gralinski,Liomar A. A. Neves,Olga Tiniakova |
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Abstract
Since the classical experiments of Goldblatt et al. (1934), there is clear evidence that the ischemia of the kidneys causes elevation of blood pressure by activation of the renin–angiotensin system. The principle can be used both for acute and chronic hypertension. In rats acute renal hypertension is induced by clamping the left renal artery for 4 h. After reopening of the vessel, accumulated renin is released into circulation. The protease renin catalyzes the first and rate-limiting step in the formation of angiotensin II leading to acute hypertension. The test is used to evaluate antihypertensive activities of drugs.
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Coronary Drugs |
Michael Gralinski,Liomar A. A. Neves,Olga Tiniakova |
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Abstract
The isolated heart–lung of the dog was introduced by Knowlton and Starling (1912). Since then, the dog model has been used for many physiological and pharmacological studies (Krayer 1931; Krayer and Mendez 1942; Somani and Blum 1966; Takeda et al. 1973; Ishikawa et al. 1978, 1983; Ono and O’Hara 1984; Ono et al. 1984; Caffrey et al. 1986; Hausknecht et al. 1986; Fessler et al. 1988; Seifen et al. 1987, 1988; Naka et al. 1989). More recently, the rat model has been preferred (Dietz 1984, 1987; Onwochei et al. 1987; Onwochei and Rapp 1988; Kashimoto et al. 1987, 1990, 1994, 1995; Fukuse et al. 1995).
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Calcium Uptake Inhibition Activity |
Michael Gralinski,Liomar A. A. Neves,Olga Tiniakova |
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Abstract
Cellular calcium flux is regulated by receptor-operated and voltage-dependent channels, which are sensitive to inhibition by calcium entry blockers. The term calcium antagonist was introduced by Fleckenstein (1964, 1967) when two drugs, prenylamine and verapamil, originally found as coronary dilators in the Langendorff experiment, were shown to mimic the cardiac effects of simple Ca. withdrawal, diminishing Ca.-dependent high-energy phosphate utilization, contractile force, and oxygen requirement of the beating heart without impairing the Na.-dependent action potential parameters. These effects were clearly distinguishable from .-receptor blockade and could promptly be neutralized by elevated Ca., .-adrenergic catecholamines, or cardiac glycosides, measures that restore the Ca. supply to the contractile system. In the following years, many Ca. antagonists were introduced to therapy. Specific Ca. antagonists interfere with the uptake of Ca. into the myocardium and prevent myocardial necrotization arising from deleterious intracellular Ca. overload. They act basically as specific inhibitors of the slow transsarcolemnal Ca. influx but do not or only slightly affect the fast Na. curren
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Anti-Arrhythmic Activity |
Michael Gralinski,Liomar A. A. Neves,Olga Tiniakova |
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Abstract
Guidelines for the study of arrhythmias in man and animals regarding the experimental design as well as the classification, quantification, and analysis were given as the Lambeth Conventions by Walker et al. (1988).
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Methods to Induce Cardiac Hypertrophy and Insufficiency |
Michael Gralinski,Liomar A. A. Neves,Olga Tiniakova |
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Abstract
Animal models of cardiac hypertrophy and insufficiency have been reviewed by Hasenfuss (1988), Muders and Elsner (2000), Vanoli et al. (2004), Patten and Hall-Porter (2009), Dubi and Arbel (2010), Gomes et al. (2013), and Szymanski et al. (2012).
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Positive Inotropic Activity (Cardiac Glycosides) |
Michael Gralinski,Liomar A. A. Neves,Olga Tiniakova |
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Abstract
Biological standardization of cardiac glycosides was necessary as long as the drugs used in therapy were plant extracts or mixtures of various glycosides. They were standardized in units of an international standard. Some of the pharmacological methods used for these purposes and adopted by many pharmacopoeias have nowadays . only. This holds true for the frog method and the pigeon method (Burn et al. 1950).
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Effects on Blood Supply and on Arterial and Venous Tonus |
Michael Gralinski,Liomar A. A. Neves,Olga Tiniakova |
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Abstract
The Mongolian gerbil (.) is extremely susceptible to carotid occlusion because of the peculiar anatomical occurrence of an incomplete circle of Willis without posterior communicating artery and a frequently rudimentary anterior communicating artery. Clamping of both carotid arteries induces a bilateral temporary brain ischemia (Levine and Sohn 1969; Bosma et al. 1981; Mršulja et al. 1983; Hossman et al. 1983; Chandler et al. 1985). This pathological animal model allows the simulation of circulatory disturbances in the human brain. The hippocampus is one of the most vulnerable regions of the brain to ischemia and anoxia. The gerbil is known to develop selective neuronal damage in the CA1 sector of the hippocampus following brief periods of forebrain ischemia. This damage differs from conventionally described ischemic neuronal injury because of its slow development (Ito et al. 1975; Kirono 1982; Hossman et al. 1983). The occlusion time can be varied allowing determination of various parameters, e.g., ischemia-induced amnesia.
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α- and β-Adrenoreceptor Binding |
Michael Gralinski,Liomar A. A. Neves,Olga Tiniakova |
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Abstract
.1-Adrenoceptors are widely distributed and are activated either by norepinephrine released from sympathetic nerve terminals or by epinephrine released from the adrenal medulla.
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Adenosine Receptor |
Michael Gralinski,Liomar A. A. Neves,Olga Tiniakova |
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Abstract
Adenosine, a purine nucleoside catabolite of ATP, regulates numerous effects in mammalian organ systems. The discovery by Drury and Szent-György (1929) that adenosine can affect several bodily functions inspired much research interest. Regulatory functions of adenosine are especially important when cellular energy supply fails to meet the demand. Adenosine is omnipresent; it is released by nearly all cells and is continuously formed intracellularly as well as extracellularly.
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Different Channels |
Liomar A. A. Neves,Olga Tiniakova |
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Abstract
The transient receptor potential (TRP1) ion channels are named after the role of the channels in . phototransduction (Montell 2001). The mammalian genes are encoded by at least 28 channel subunit genes (Clapham 2003; Moran et al. 2004; Clapham et al. 2005). Six protein families comprise the mammalian TRP superfamily: the classic TRPs (TRPCs), the vanilloid receptor TRPs (TRPVs), the melastatin or long TRPs (TRPMs), the mucolipins (TRPMLs), the polycystins (TRPPs), and ankyrin transmembrane protein 1 (ANKTM1, TRPA1). The TRP channel primary structures predict six transmembrane (TM) domains with a pore domain between the fifth (S5) and sixth (S6) segments and both C and N termini presumably located intracellularly (Vannier et al. 1998).
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Effect of Different Peptides |
Michael Gralinski,Liomar A. A. Neves,Olga Tiniakova |
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Abstract
Eschenhagen et al. (1997) developed a method for culturing embryonic cardiomyocytes in a collagen matrix to produce a coherently contracting three-dimensional model heart tissue that allows direct measurement of isometric contractile force.
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Na+/H+ Exchange |
Michael Gralinski,Liomar A. A. Neves,Olga Tiniakova |
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Abstract
Na./H. exchange was first described by Murer et al. (1976) in a study of intestinal and renal brush-border vesicles. The plasma membrane Na/H exchanger is an ubiquitous pH-regulating cellular ion transport system. It is driven by the Na. gradient and extrudes protons from the cytosol in exchange for extracellular Na. ions (Aronson 1985; Frelin et al. 1988; Fliegel and Dyck 1995; Orlowski and Grinstein 1997; Wakabayshi et al. 1997; Dibrov and Fliegel 1998). Six mammalian Na./H. exchangers, NHE1, NHE2, NHE3, NHE4, NHE5 (Attaphitaya et al. 1999; Szabo et al. 2000), and NHE6, have been described (Tse et al. 1994; Orlowski 1999; Counillon and Pouysségur 2000).
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NO Activity and Rho Kinase Activity |
Michael Gralinski,Liomar A. A. Neves,Olga Tiniakova |
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Abstract
The endothelium releases a labile, diffusible, vasorelaxing substance that has been termed endothelium-derived relaxing factor (EDRF) (Furchgott and Zawadzki 1980). Nitric oxide release accounts for the biological activity of endothelium-derived relaxing factor (Palmer et al. 1987; Vanhoutte 1999).
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PAF Binding and Endothelins Activity |
Michael Gralinski,Liomar A. A. Neves,Olga Tiniakova |
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Abstract
Injection of platelet-activating factor (PAF) induces a wide range of potent and specific effects on target cells, including aggregation of platelets and shock symptoms like systemic hypotension, pulmonary hypertension, increased vascular permeability, neutropenia, and thrombocytopenia. Inhalation of PAF causes immediate bronchoconstriction followed by inflammation of the airways (for further information, see section “B.1.9”).
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Patch-Clamp and Voltage-Clamp Techniques |
Michael Gralinski,Liomar A. A. Neves,Olga Tiniakova |
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Abstract
The introduction of the patch-clamp technique (Neher and Sakmann 1976) revolutionized the study of cellular physiology by providing a high-resolution method of observing the function of individual ionic channels in a variety of normal and pathological cell types. By the use of variations of the basic recording methodology, cellular function and regulation can be studied at a molecular level by observing currents through individual ionic channels (Liem et al. 1995; Sakmann and Neher 1995).
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Phosphodiesterases and the Effects of Forskolin |
Michael Gralinski,Liomar A. A. Neves,Olga Tiniakova |
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Abstract
Cyclic nucleotide phosphodiesterases (PDEs) catalyze the hydrolysis of cAMP and/or cGMP. They function with adenyl and guanylyl cyclases to regulate the amplitude and duration of responses triggered by the second messengers cAMP and cGMP. The enzyme phosphodiesterase (PDE) exists in various forms. At least 11 families of phosphodiesterases have been identified (Torphy and Page 2000; Francis et al. 2001; Maurice et al. 2003; Lugnier 2006). The properties and functions of GAF domains in cyclic nucleotide phosphodiesterases are reviewed by Zoraghi et al. (2004).
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发表于 2025-3-21 18:54:23
