The potent bronchodilator, clenbuterol, was compared to other beta adrenoceptor agonists with regard to affinity and efficacy for interaction with beta 1, and beta 2 adrenoceptors in the rat jugular vein and atria. Clenbuterol was a potent partial beta adrenoceptor agonist in both tissues based on the following observations: 1. Maximal relaxation of the jugular vein and increases in atrial rate to clenbuterol were less than maximal responses to other beta adrenoceptor agonists. 2. Clenbuterol antagonized responses to the stronger agonist, isoproterenol, in both tissues and 3. the equilibrium dissociation constant for clenbuterol approximated the ED50 concentration for vascular relaxation and increases in atrial rate, a characteristic of some, but not all, partial agonists. Relative to other beta adrenoceptor agonists, clenbuterol showed high affinity toward both beta 1 and beta 2 adrenoceptors and selectively toward beta 2 adrenoceptors. Equilibrium dissociation constants were 38 and 6.3 nM for beta 1 and beta 2 adrenoceptors, respectively. The high affinity of clenbuterol toward beta 1 and beta 2 adrenoceptors was coupled to a low relative efficacy of clenbuterol to activate either beta 1 or beta 2 adrenoceptors. Most beta 2 adrenoceptor agonists such as isoproterenol or salbutamol require approximately 1-3% adrenoceptor occupation for 40-50% relaxation of the jugular vein whereas clenbuterol required approximately 100% adrenoceptor occupation for a similar response. Thus, based on our analysis, the high agonist potency of clenbuterol results primarily from the high affinity toward beta adrenoceptors rather than efficient activation of the adrenoceptor as occurs with isoproterenol or salbutamol.
Rat portal, mesenteric, renal, and femoral veins possess functionally responsive circular and longitudinal smooth muscle layers in vitro. In contrast to the dominant rhythmically active longitudinal muscle of portal veins, rat longitudinal mesenteric veins lacked rhythmic activity and developed maximal force equivalent to that of mesenteric circular muscle. Renal and femoral veins exhibited predominantly circular smooth muscle responses. Rat veins must be subjected to between 1 g (renal and femoral) and 4 g (circular portal and mesenteric) of passive forse for optimal responsiveness. Contractile response to vasoactive agent including carbamylcholine, serotonin, and norepinephrine was quantitatively different among veins. Femoral veins developed greater maximal force in response to norepinephrine than to KCL, and the responses to norepinephrine were not altered by cocaine. In contrast, cocaine markedly potentiated responses to norepinephrine in portal, mesenteric, and renal veins and, to a lesser extent, in the mesenteric artery. These data demonstrate heterogeneity in rat venous tissue and suggest that neuronal innervation may markedly influence responses to norepinephrine in some, but not all, rat blood vessels.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.