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  • 1
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Science Pty
    Clinical and experimental pharmacology and physiology 32 (2005), S. 0 
    ISSN: 1440-1681
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: 1. Prostaglandin D (DP) receptor agonists have been shown to induce hypotension in rat models, possibly via peripheral vasodilation. However, it is not known which tissues and organs are most responsive.2. In the present study, BW245C, a DP receptor-selective agonist, was administered to Inactin (Sigma, St Louis, MO, USA)-anaesthetized rats. Animals received three serial i.v. infusions (17 min each) of either BW245C (escalating doses of 0.3, 3 and 30 μg/kg; n = 6) or vehicle (6% ethanol in normal saline; n = 6). Mean arterial pressure (MAP) and heart rate were monitored continuously and regional blood flow was determined by the radionuclide-labelled microsphere method at baseline and at the end of each infusion.3. It was found that BW245C dose-dependently reduced MAP; blood flow increased in forelimb skeletal muscle and skin, resulting in decreases in the regional vascular resistance (RVR) of skeletal muscle to −6 ± 13, −53 ± 11 and −68 ± 6% of baseline following 0.3, 3 and 30 μg/kg BW245C, respectively (P 〈 0.05 vs vehicle treatment for the two higher doses), and skin to −29 ± 8, −55 ± 8 (P 〈 0.05) and −30 ± 16% of baseline, respectively. Relative to vehicle, blood flow and RVR for brain, heart, lung, liver, stomach and kidney were not significantly affected by BW245C.4. These results demonstrate that the hypotension resulting from DP receptor activation in the rat is mediated primarily through vasodilation of arterioles of skeletal muscle independent of changes in blood flow to vital organs.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1440-1681
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: 1. Activation of dopamine (DA) receptors produces cardiovascular responses such as vasodilation and hypotension. However, knowledge of the role of specific dopamine receptor subtypes (especially D3 and D4) in the cardiovascular system is limited. The objective of the present study was to characterize the haemodynamic and cardiac responses to agonists with selectivity for D1, D2, D3 and D4 receptor subtypes.2. Inactin-anaesthetized rats were instrumented to measure regional haemodynamic and cardiac contractility responses with slow intravenous infusion of agonists.3. Fenoldopam (a D1 receptor agonist) decreased (P 〈 0.05) renal vascular resistance beginning at a dose of 3 µmol/kg. Infusion of PNU-95666E (a D2 receptor agonist) produced dose-dependent decreases (P 〈 0.05) in mean arterial pressure (MAP), heart rate (HR) and hindquarter vascular resistance (HQVR). Administration of BP897 (a partial D3 receptor agonist) decreased (P 〈 0.05) MAP and HQVR at 3 µmol/kg. PD168077 (a D4 receptor agonist) caused significant increases in HQVR at 1 µmol/kg. None of the compounds tested elicited significant changes in cardiac contractility.4. Using selective agonists of dopamine receptor subtypes, the present studies characterize distinct cardiovascular effects in anaesthetized rats. Consistent with its well-defined effects as a D1 receptor agonist, fenoldopam administration resulted in renal vasodilation. Similar to earlier studies using the non-selective D2-like receptor agonist quinpirole, selective agonism at the D2 receptor using PNU-95666E resulted in bradycardia, hindquarter vasodilation and decreases in arterial pressure. Partial agonism at the D3 receptor with BP897 had no effect on heart rate, but did produce depressor responses driven by decreases in HQVR. Conversely, agonism of the D4 receptor using PD168077 resulted in modest hindquarter vasoconstriction that was not dose dependent. Hence, by comparison, agonism of the D4 receptor has little effect in the cardiovascular system of the rat relative to the other dopamine receptor subtype agonists tested.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-2013
    Keywords: Vascular smooth muscle ; Calcium ; Smooth muscle mechanics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Stimulation of swine carotid artery medial fibers with 110 mM KCl at 37°C results in increases in myosin light chain (MLC) phosphorylation levels and maximal shortening velocity (V o) during the period of stress development. During the period of stress maintenance, MLC phosphorylation levels andV o are not maintained, but fall to suprabasal levels, resulting in a correlation between MLC phosphorylation andV o and suggesting that MLC phosphorylation regulatesV o. This study identifies other conditions of KCl depolarization of swine carotid medial fibers in which this relationship between MLC phosphorylation andV o is altered. A decrease in temperature from 37° to 23°C results in a similar magnitude of stress maintenance in response to 110 mM KCl and similar levels of MLC phosphorylation, but a reduction inV o by approximately 50%. This differential effect of temperature onV o and MLC phosphorylation results in a downward shift in the slope of the regression line describing the relationship between these two parameters. Decreasing [KCl] to 40 mM in the stimulating solution results again in similar magnitudes of miantained stress. MLC phosphorylation levels are not transient, but maintained at a constant value andV o is transient at levels approximately 50% of those at 110 mM KCl at 37°C. This results in a complete lack of correlation between MLC phosphorylation andV o. Thus stress can be developed to equal magnitudes under differing activation conditions with dissimilar patterns of MLC phosphorylation andV o. Therefore, there is not a strict relationship between MLC phosphorylation andV o in all cases.
    Type of Medium: Electronic Resource
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