Circulating and tissue angiotensin systems.

Abstract

Angiotensin has many different actions, most of which relate, either directly or indirectly, to the regulation of blood pressure, fluid, and electrolyte homeostasis (1, 2). In addition to potent vasoconstrictor effects, actions ofangiotensin on vasculature include the stimulation ofprostaglandin release (3), the modulation of angiotensin receptor number (4), and the stimulation of angiogenesis (5). Angiotensin also has important actions on the central and peripheral nervous systems, the adrenal, kidney, intestine, and heart (6-1 1). Given these multiple diverse actions of angiotensin, two important questions are (a) which of these actions represent normal physiological events, and (b) whether such actions may assume a pathogenic role. These questions have recently been placed in sharper focus by the clinical application of inhibitors of the renin-angiotensin system (RAS),' and in particular, the use of converting enzyme inhibitors (CEIs) for the treatment of hypertension. Any attempt to answer these questions requires an accurate concept ofthe RAS. The purpose ofthis review is to discuss new concepts concerning angiotensin production by the circulating RAS, how these relate to angiotensin production within tissues, and the possible mechanisms by which CEIs lower blood pressure. The study of tissue angiotensin systems is still at an early stage. In this review I have attempted to synthesize a coherent model of the interaction between the circulating and tissue angiotensin systems, which might assist in the interpretation of new developments in this area. Circulating RASAt the present time, the prevailing view holds that the circulating RAS is primarily an endocrine system designed for the general mediation, through the systemic circulation, of the effects of renin on angiotensin production in plasma (12,13). This concept can be summarized as follows: renin released by the kidney circulates in plasma, where it cleaves angiotensinogen to generate angiotensin I (Al).

The Relationship of Left Ventricular Mass to Endothelium-Dependent Vasodilation of the Brachial Artery in Patients with Hypertension

“…The renin-angiotensin system, which is one of the important factors underlying the mechanism of hypertension, is expressed locally in many tissues, including the heart [36, 37, 38], and this local renin-angiotensin system plays an important role in the cardiovascular disorders such as hypertrophy [37]and ventricular remodeling after myocardial infarction [38]. It has been shown that angiotensin II promotes the generation of superoxide radical by NADH/NADPH oxidase activation [39, 40], and free radical has been shown not only to cause the impairment of endothelium-dependent vasodilation [15]but also to mediate hypertrophic responses in myogenic cells [41].…”

Enalapril Increases Antioxidant Enzyme Activity in Renal Cortical Tissue of Five-Sixths- Nephrectomized Rats

“…A direct effect of enalapril on the extracellular matrix protein synthesis is achieved by its ability to reduce the level of the protein kinase C agonist AngII by inhibiting the conversion of AngI to AngII by ACE. However, treatment with enalapril does not completely block the synthesis of AngII, since several enzymes other than ACE can convert AngI to AngII or can cleave angiotensinogen to release AngII directly [26]. …”

Mast cells: A unique source of renin

“…The rate-limiting step in the formation of angiotensin II (ANG II) is the proteolytic action of renin, which cleaves angiotensinogen (Aogen) to the intermediate angiotensin I (ANG I). ANG I is then converted to ANG II by angiotensin-converting enzyme (ACE) at the endothelial surface (2,3).…”