Removal of endothelial cells on rings of rat aorta increased the sensitivity to the selective alpha-1 adrenoceptor agonist phenylephrine, to the nonselective alpha adrenoceptor agonist norepinephrine and to the selective alpha-2 adrenoceptor agonist clonidine. In the case of the first two, which are strong agonists for the alpha-1 adrenoceptor-mediating contraction, removal of endothelium increased sensitivity 4- and 6-fold at the EC30 level, but produced little or no increase in maximum. In the case of clonidine, a partial agonist for the alpha-1 adrenoceptor, which gave only about 15% of the maximum given by phenylephrine on endothelium-containing rings, removal of the endothelium not only shifted the curve to the left but also increased the maximum to about 50% of that given by phenylephrine. The depression of sensitivity to these agonists in rings with endothelium appeared to be due to the vasodepressor action of endothelium-derived relaxing factor (EDRF), as hemoglobin, a specific blocking ...
Ample experimental evidence supports the existence of two distinct types of vasoconstrictor α-adrenoceptors in vascular smooth muscle at postjunctional sites, showing similarities with α1 and α2-adrenoceptors. Especially in vivo, the characterization of an α2-adrenoceptor mediating an increase in diastolic pressure has been most successful. In this respect the model of the pithed rat has been employed most frequently (for reviews see [1, 2]).. At present, the agents cirazoline, (−) phenylephrine, (±)-erythro-methoxamine, (−)-amidephrine, SKF89748, St587 and Sgd 101/75 fulfil the criteria for selective α1-adrenoceptor agonists; their log dose-vasopressor effect curves are virtually unaffected by previous treatment with yohimbine or rauwolscine (selective dose in pithed rats: 1 mg/kg), whereas prazosin (selective dose in pithed rats: 0.1 mg/kg) causes an appreciable parallel rightward displacement. The reverse holds true for the stimulants B-HT 920, B-HT 933, B-HT 958, UK-14304, ...
Amibegron, a highly selective β3-adrenoceptor agonist originated by Sanofi (now sanofi-aventis), stimulates neuronal activity in a specific area of the
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TY - JOUR. T1 - Cooling and α1- and α2-adrenergic responses in cutaneous veins. T2 - Role of receptor reserve. AU - Flavahan, Nicholas. AU - Lindblad, L. E.. AU - Verbeuren, T. J.. PY - 1985. Y1 - 1985. N2 - Experiments were designed to determine the effects of cooling on α1- and α2-adrenergic responses in isolated canine cutaneous veins. Rings of saphenous veins were suspended for isometric tension recording in physiological salt solution. Cooling (from 37 to 24°C) augmented contractions to norepinephrine under control conditions and after α1-adrenergic blockade (prazosin) but not following α2-adrenergic blockade (rauwolscine). Cooling augmented contractions evoked by the α2-adrenergic agonists B-HT 920 and UK 14304 but did not affect responses to the full α1-adrenergic agonist phenylephrine. These experiments suggest that cooling augments α2-adrenergic responsiveness without affecting α1-adrenergic responsiveness. However, the contractions evoked by the partial α1-adrenergic ...
Tablet. Patients who engage in potentially hazardous activities, such as operating machinery or driving, should be advised of a potential sedative effect of clonidine. Patients should be cautioned against interruption of clonidine hydrochloride therapy without a physicians advice.. Epidural Injection. Patients should be instructed about the risks of rebound hypertension and warned not to discontinue clonidine except under the supervision of a physician. Patients should notify their physician immediately if clonidine administration is inadvertently interrupted for any reason. Patients who engage in potentially hazardous activities, such as operating machinery or driving, should be advised of the potential sedative and hypotensive effects of epidural clonidine. They should also be informed that sedative effects may be increased by CNS-depressing drugs such as alcohol and barbiturates, and that hypotensive effects may be increased by opiates.. ...
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