Chess-Williams R G, Williamson K L, Broadley K J
Department of Pharmacology and Therapeutics, University of Liverpool, UK.
Fundam Clin Pharmacol. 1990;4(1):25-37. doi: 10.1111/j.1472-8206.1990.tb01014.x.
Phenylephrine produced concentration-related positive inotropic responses in isolated left atria and papillary muscles of guinea-pigs and rats. In rat tissues, these responses were unaffected by propranolol but antagonized by prazosin and therefore mediated via alpha 1-adrenoceptors. The alpha 1-adrenoceptor agonist methoxamine also exerted positive inotropic effects in these rat tissues. The maximum alpha-adrenoceptor-mediated effect of methoxamine (relative to the isoprenaline maximum) was greater than that of phenylephrine in left atria (in the presence of propranolol), whereas in papillary muscles phenylephrine exerted the greater maximum. In guinea-pig papillary muscles, the response to phenylephrine was unaffected by prazosin but was antagonized by propranolol and therefore caused by stimulation of beta-adrenoceptors. Methoxamine had no effect in guinea-pig papillary muscles. Guinea-pig left atria produced biphasic concentration-response curves for phenylephrine, the lower portion being antagonized by phentolamine and was therefore alpha-adrenoceptor-mediated, while the upper portion was antagonized by propranolol and therefore beta-adrenoceptor-mediated. Methoxamine exerted a small inotropic response, the maximum of which was similar to that of the first component of the phenylephrine response. Phenylephrine was a partial agonist for the cardiac beta-adrenoceptor. The density of rat ventricular alpha-adrenoceptors was 4 times greater than beta-adrenoceptor density, as measured by [3H]-prazosin and [3H]-dihydroalprenolol binding. This explains why the responses of rat papillary muscles were alpha-adrenoceptor-mediated. In contrast, the density of beta-adrenoceptor binding sites in guinea-pig ventricles was 6 times greater than the alpha-adrenoceptor density. This explains why the phenylephrine responses were beta-adrenoceptor-mediated in guinea-pig papillary muscles. In the left atria of guinea-pigs, which displayed both alpha- and beta-adrenoceptor-mediated responses, the densities of alpha- and beta-adrenoceptor binding sites were similar. Thus, phenylephrine exerts positive inotropic effects through alpha- or beta-adrenoceptors depending upon their relative densities.
去氧肾上腺素在豚鼠和大鼠的离体左心房及乳头肌中产生浓度相关的正性肌力反应。在大鼠组织中，这些反应不受普萘洛尔影响，但被哌唑嗪拮抗，因此是通过α1 -肾上腺素能受体介导的。α1 -肾上腺素能受体激动剂甲氧明在这些大鼠组织中也发挥正性肌力作用。在左心房中（存在普萘洛尔时），甲氧明的最大α -肾上腺素能受体介导效应（相对于异丙肾上腺素的最大值）大于去氧肾上腺素，而在乳头肌中去氧肾上腺素发挥的最大效应更大。在豚鼠乳头肌中，对去氧肾上腺素的反应不受哌唑嗪影响，但被普萘洛尔拮抗，因此是由β -肾上腺素能受体刺激引起的。甲氧明对豚鼠乳头肌无作用。豚鼠左心房对去氧肾上腺素产生双相浓度 -反应曲线，较低部分被酚妥拉明拮抗，因此是α -肾上腺素能受体介导的；而较高部分被普萘洛尔拮抗，因此是β -肾上腺素能受体介导的。甲氧明产生小的正性肌力反应，其最大值与去氧肾上腺素反应的第一成分相似。去氧肾上腺素是心脏β -肾上腺素能受体的部分激动剂。通过[3H] -哌唑嗪和[3H] -二氢阿普洛尔结合测定，大鼠心室α -肾上腺素能受体密度比β -肾上腺素能受体密度大4倍。这解释了为什么大鼠乳头肌的反应是α -肾上腺素能受体介导的。相反，豚鼠心室中β -肾上腺素能受体结合位点的密度比α -肾上腺素能受体密度大6倍。这解释了为什么在豚鼠乳头肌中去氧肾上腺素的反应是β -肾上腺素能受体介导的。在显示α -和β -肾上腺素能受体介导反应的豚鼠左心房中，α -和β -肾上腺素能受体结合位点的密度相似。因此，去氧肾上腺素根据α -和β -肾上腺素能受体的相对密度通过α -或β -肾上腺素能受体发挥正性肌力作用。
