Interactions between endothelin-1 and the renin–angiotensin–aldosterone system

Abstract

The renin-angiotensin-aldosterone (RAA) system and the endothelin (ET) system entail the most potent vasopressor mechanisms identified to date. Although they were studied in depth in relation to arterial hypertension and cardiovascular diseases, limited information on their interrelationships in causing hypertension and related target organ damage exists. The identification of consensus sequences for jun in the regulatory region of the preproendothelin-1 (ppET-1) gene raised the possibility of its transcriptional regulation by angiotensin II (Ang II). This was confirmed by the finding that stimulation with Ang II of cultured vascular smooth muscle cells (VSMCs) and endothelial cells (ECs) induced expression of the ppET-1 gene and synthesis of ET-1. Endogenously produced ET-1 was found to contribute to the hypertrophic response of cardiomyocytes to Ang II and thereby to cardiac hypertrophy. Furthermore, ET-1 exerts multifaceted effects on the RAA system, such as dose-dependent inhibition of renin synthesis, and stimulation of aldosterone secretion. The finding of abundant specific ET-1 receptors in the adrenocortical zona glomerulosa (ZG) suggested a direct secretagogue effect of ET-1. In rats, ETB receptors mediate such an effect, whilst in humans, both ETA and ETB receptor subtypes intervene in regulating the transcription of the aldosterone synthase gene. In addition, ET-1 stimulates DNA synthesis and proliferation of ZG cells via ETA receptors and, therefore, might play a role in cell turnover of the normal adrenal cortex and in the onset of adrenal tumours. Studies on the in vivo interactions between ETs and the RAA system have given conflicting results, insofar as some suggested a participation of ET-1 in the pressor and cellular effects of exogenously administered Ang II, whereas others did not in the transgenic TGR(Ren 2m)27 rats and in the two-kidney, one clip.

Effect of Breed on Plasma Endothelin‐1 Concentration, Plasma Renin Activity, and Serum Cortisol Concentration in Healthy Dogs

“…Newfoundlands, on the other hand, had low renin activity and high ET‐1 as well as NT‐proBNP concentration 11. Natriuretic peptides are known to suppress RAAS activation in dogs as well as people,32, 33 and ET‐1 has been suggested to inhibit renin production, but the interaction between hormonal systems is complex 34. Taken together, the present results indicate that if ET‐1 and natriuretic peptides are high, the renin activity is low and vice versa.…”

Selective Endothelin-A Receptor Antagonism Reduces Proteinuria, Blood Pressure, and Arterial Stiffness in Chronic Proteinuric Kidney Disease

“…[27][28][29] Furthermore, we have shown recently that acute ET A receptor antagonism can reduce proteinuria by an additional Ϸ30% on top of that achieved with optimal treatment with inhibitors of the renin-angiotensin system in subjects with proteinuric CKD. 14 The current study suggests that these effects are maintained longer term and are of a similar magnitude.…”

Plasma biomarkers as predictors of recurrence of atrial fibrillation

“…11,12 ET-1 affects the RAAS by stimulating aldosterone (ALD) secretion 13 and increases the release of natriuretic peptides, while these peptides inhibit ET-1 secretion. [12][13][14] High activity of angiotensin II, ET-1, and ALD promotes cardiac fibrosis, 6,15 thus participating in the patophysiology of AF through atrial structural remodeling.…”

“…[12][13][14] High activity of angiotensin II, ET-1, and ALD promotes cardiac fibrosis, 6,15 thus participating in the patophysiology of AF through atrial structural remodeling.…”