Angiotensin II and the Heart

Abstract

Abstract-The active end product of the renin-angiotensin system, angiotensin II (Ang II), through the activation of specific Ang II receptors, regulates cardiac contractility, cell coupling, and impulse propagation and is involved in cardiac remodeling, growth, and apoptosis. We review these subjects, as well as the second messengers that are involved, and the synthesis of Ang II in the heart under normal and pathological conditions. Finally, we discuss the possibility that there is an intracrine renin-angiotensin system in the heart that plays a role in the control of cell communication and inward Ca 2ϩ current. (Hypertension. 2000;35:1183-1188.)Key Words: angiotensin Ⅲ heart Ⅲ hypertrophy Ⅲ receptors, angiotensin Ⅲ renin Ⅲ signal transduction A ngiotensin (Ang) II, through the activation of specific Ang II receptors, regulates cardiac contractility, cell communication, and impulse propagation. In addition, Ang II is involved in cardiac remodeling, growth, and apoptosis. In the past 10 years, the concept of a local renin-angiotensin system (RAS) located in the heart and other organs has gradually gained support, particularly with the demonstration that elements of the RAS cascade (ie, renin, angiotensinogen, Ang I, Ang II, and angiotensin-converting enzyme [ACE]) are present in tissues. 1,2 In the present article, we review up-to-date evidence that Ang II receptor activation is related to the different actions of Ang II in the heart. We also discuss renin-and ACE-dependent generation of Ang II at cardiac tissue sites and the evidence that there is an intracrine RAS in the heart. Ang II generation through alternative pathways (eg, through cathepsin D, tonin, or chymase) as well as the cardiac effects of other angiotensin metabolites, eg, Ang III, Ang IV, and Ang-(1-7), and their receptors are outside the scope of this review and will not be discussed. Ang II ReceptorsThe effect of Ang II on cardiac tissue is related to the activation of 2 specific receptors, AT 1 and AT 2 . 3,4 The AT 1 receptor has 2 subtypes: AT 1A and AT 1B . 5 AT 1A receptors are major blood pressure regulators and potent growth stimulators in cardiomyocytes in vivo, whereas AT 1B receptors are involved in the control of vascular tone when AT 1A receptors are absent. 6 Ang II receptors are 7-transmembrane domain receptors whose primary structures have been established by molecular cloning. [7][8][9] The activation of the receptor is coupled to several intracellular proteins, starting with a G protein. 10 The receptor domains that couple to G proteins involve the second and third cytosolic loops and the proximal segment of the carboxy-terminal domain. 10 -12 In the rat, AT 1A , AT 1B , and AT 2 receptors are located on chromosomes 17, 2, and X, respectively. 11 Samyn et al 13 have demonstrated that cardiac AT 1 receptor gene expression is relatively unchanged during fetal and newborn life and that AT 2 receptor mRNA expression is high during fetal development and decreases rapidly after birth. Administration of Ang II to a rat whole embryo c...

Comparative Effects of a Novel Angiotensin-Converting Enzyme Inhibitor versus Captopril on Plasma Angiotensins after Myocardial Infarction

“…Additionally, ACE inhibitors attenuate not only the production of Ang II at a systemic and tissue level, but they also allow the accumulation of bradykinin because they inhibit its degradation [20,21,22,23]. Animal studies have shown that the inhibition of bradykinin degradation contributes more to the reduction in blood pressure than the inhibition of Ang II formation by ACE inhibitors [24,25,26,27].…”

Physiology of Local Renin-Angiotensin Systems

“…This suggests that at least in some species, the heart is a site of extrarenal renin production. Other authors have suggested that, whereas renin is not synthesized in the heart under physiological conditions, renin gene expression may be turned on in pathophysiological situations (147). It is interesting to note in this context that an additional truncated renin mRNA has been described in heart tissue which lacks the prefragment of preprorenin and results in the formation of a truncated prorenin protein termed exon 1A renin (103,541).…”

The Interaction between the Renin-Angiotensin System and Vascular Endothelial Growth Factor in the Pathogenesis of Retinal Neovascularization in Diabetes

“…In turn, the terminal two amino acids of angiotensin I are cleaved by angiotensin-converting enzyme (ACE) to yield Ang II, the effector molecule of the renin-angiotensin system (RAS). The presence of a local, as distinct from a systemic RAS, has been established in several organs including the heart, adrenal gland, thymus and ovary [7, 8, 9, 10, 11, 12]. This is also true for the eye, following the identification of RAS components including angiotensinogen, renin and ACE within the eyes of humans, rats and other mammals [13, 14, 15, 16].…”