Functional evidence that in the cardiovascular system AT angiotensin II receptors are AT prejunctionally and AT postjunctionally

Abstract

Numerous studies have shown that angiotensin II causes vasoconstriction both by a direct action on smooth muscle cells (postjunctional effect) and indirectly through the facilitation of noradrenaline release from postganglionic sympathetic neurons (prejunctional effect). The receptors through which angiotensin II exerts its actions were first divided into AT1 and AT2 subtypes. A further subdivision of AT1 receptors into AT1A and AT1B subtypes was based on cloning and receptor binding studies: AT1A showed a high affinity for losartan, but low affinity for PD123319, while AT1B receptors showed nearly 100-fold lower affinity for losartan and 10,000-fold higher affinity for PD123319 relative to AT1 sites. The present review deals with functional evidence supporting the existence of AT1A and AT1B subtypes in the cardiovascular system. Taken together, all the functional results obtained in vivo and in vitro-in a wide variety of vascular tissues from different species-allow one to conclude that angiotensin II AT1 receptors are different pre- and postjunctionally and also that prejunctional and postjunctional angiotensin II receptors most probably belong to AT1B and AT1A subtypes, respectively.