An analysis of the effects of urethane on cardiovascular responsiveness to catecholamines in terms of its interference with Ca++ mobilization from both intra and extracellular pools

Abstract

Urethane (1 X 10(-2) - 1 X 10(-1) M) reduced, in a concentration-dependent manner, both intra and extracellular Ca++ dependent noradrenaline-induced contractions of perfused rabbit ear artery as well as the tonic contractions produced by perfusion with high K+ solution. However, a quantitative analysis of the data indicated that for urethane concentrations similar to those found in plasma during anesthesia urethane antagonism is confined to noradrenaline-induced contractions which depend upon the mobilization of Ca++ from intracellular storage sites. In KCl-contracted arteries, urethane enhanced the relaxant effects of isoprenaline. - Urethane reduced the amplitude of contractions of spontaneously beating guinea-pig right atrium at concentrations which have only a limited effect on frequency. In addition, it decreased in a concentration-dependent manner the amplitude of isoprenaline-activated electrically driven, and K+ depolarized guinea-pig right ventricular strips. Urethane had no effect on the chrono and inotropic actions of isoprenaline on cardiac preparations. In in vivo experiments the chronotropic response to low doses of isoprenaline was significantly higher in urethane-treated as compared to unanesthetized rats. The higher dose of isoprenaline tested produced a significant fall in systolic blood pressure in urethane-anesthetized rats. A significant correlation exists between the chronotropic response to isoprenaline and resting heart rate values in urethane-anesthetized rats. These results indicate that urethane, at concentrations similar to those found in plasma during anesthesia selectively interferes with mobilization of Ca++ from intracellular storage sites. In addition, the interference of urethane anesthesia with the isoprenaline chronotropic effect 'in vivo' cannot be explained by a direct interference of urethane with beta-adrenoceptors at cardiac level.

Effects of RVLM Stimulation on Blood Pressure and Vasopressin-Like Levels in Brain Sites and Plasma are an Anesthetic Dependent.

“…The urethane hypotensive effect here is in good agreement with several lines of studies which have shown a reduction in the basal BP of the rats [30,31]. There are many proposed mechanisms for urethane hypotensive effects.…”

“…There are many proposed mechanisms for urethane hypotensive effects. One of the mechanisms proposed at a cellular level, interference of urethane with Ca ++ availability for contraction of vascular and tracheal smooth muscle [31,32], although Maggi et al [31] believed that interference with transmembrane Ca ++ fluxes would not seem to be a factor since this only occurs at concentrations higher than required for anesthesia. Another proposal mechanism is that urethane anesthesia inhibits cardiovascular responses that are mediated via peripheral and central α2-adrenoceptors [33].…”

Enhanced inhibitory control by neuropeptide Y Y5 receptor blockade in rats

“…Alternatively, this difference may be due to the use of anesthetized preparations for the electrophysiological experiments. Urethane is known to affect multiple neurotransmitter-gated ion channels (Hara and Harris 2002), thus shifting the dose-response curve of several drugs (e.g., Armstrong et al 1982;Maggi et al 1984;West 1998).…”

Suitability of urethane anesthesia for physiopharmacological investigations in various systems. Part 2: Cardiovascular system

“…Urethane anesthesia, depending upon dose, route of administration and species can either reduce or have no effect on blood pressure; heart rate may be reduced, unaffected or even increased as compared to controls 6, ~5, 17,18,20,27,29,32,43,52 These discrepancies have led to disparate conclusions about the suitability of urethane anesthesia for physiopharmacological investigation at cardiovascular level.…”