Potassium Intake Prevents the Induction of the Renin-Angiotensin System and Increases Medullary ACE2 and COX-2 in the Kidneys of Angiotensin II-Dependent Hypertensive Rats.

Alexis A Gonzalez,Carlos P Vio,Matias Gallardo,Carlos Cespedes

doi:10.3389/fphar.2019.01212

Abstract

In angiotensin II (Ang II)-dependent hypertensive rats there is an increased expression of proximal tubule angiotensinogen (AGT), collecting duct renin and angiotensin converting enzyme (ACE), which contributes to intratubular Ang II formation. Ang II acts on Ang II type 1 receptors promoting sodium retention and vasoconstriction. However concurrently, the ACE2-Ang-(1–7) axis and the expression of kallikrein and medullary prostaglandins counteract the effects of Ang II, promoting natriuresis and vasodilation. Human studies demonstrate that dietary potassium (K+) intake lowers blood pressure. In this report we evaluate the expression of AGT, ACE, medullary prorenin/renin, ACE2, kallikrein and cyclooxygenase-2 (COX-2) in Ang II-infused rats fed with high K+ diet (2%) for 14 days. Dietary K+ enhances diuresis in non-infused and in Ang II-infused rats. The rise in systolic blood pressure in Ang II-infused rats was attenuated by dietary K+. Ang II-infused rats showed increased renal protein levels of AGT, ACE and medullary prorenin and renin. This effect was attenuated in the Ang II + K+ group. Ang II infusion decreased ACE2 compared to the control group; however, K+ diet prevented this effect in the renal medulla. Furthermore, medullary COX-2 was dramatically induced by K+ diet in non-infused and in Ang II infused rats. Dietary K+ greatly increased kallikrein immunostaining in normotensive rats and in Ang II-hypertensive rats. These results indicate that a high K+ diet attenuates Ang II-dependent hypertension by preventing the induction of ACE, AGT and collecting duct renin and by enhancing medullary COX-2 and ACE2 protein expression in the kidney.

Highlights

The activity of the systemic renin-angiotensin system (RAS) promotes vasoconstriction and sodium reabsorption primarily by angiotensin II (Ang II)-dependent stimulation of aldosterone release and by activation of distal nephron sodium channels (Masilamani et al, 1999; ChaszczewskaMarkowska et al, 2016)
Accumulated evidence demonstrated the presence of an intrarenal RAS (Navar et al, 2011) whose activity is stimulated in Ang II-dependent hypertension (Liu et al, 2011) and in salt induced renal injury (Kobori et al, 2001; Prieto-Carrasquero et al, 2004; Susic et al, 2009). mRNA angiotensinogen (AGT) expression can be detected in the proximal tubules and is augmented in Ang II-infused rats (Kobori et al, 2004)
In this study we demonstrated that Ang II-dependent blood pressure responses at day 14 of treatment are partially prevented by dietary supplementation of K+

Summary

Introduction

The activity of the systemic renin-angiotensin system (RAS) promotes vasoconstriction and sodium reabsorption primarily by angiotensin II (Ang II)-dependent stimulation of aldosterone release and by activation of distal nephron sodium channels (Masilamani et al, 1999; ChaszczewskaMarkowska et al, 2016). Accumulated evidence demonstrated the presence of an intrarenal RAS (Navar et al, 2011) whose activity is stimulated in Ang II-dependent hypertension (Liu et al, 2011) and in salt induced renal injury (Kobori et al, 2001; Prieto-Carrasquero et al, 2004; Susic et al, 2009). Renin is expressed in the CD and is upregulated in Ang II-dependent hypertension (Prieto-Carrasquero et al, 2004) This evidence, along with the augmented expression of angiotensin converting enzyme (ACE) in animal models of hypertension (GonzalezVillalobos et al, 2009), indicates that intrarenal RAS activation has a role in intratubular Ang II formation. In Ang II-infused rats the concentrations of intratubular Ang II are much higher than expected by plasma accumulation (Vonthun et al, 1994; Navar et al, 2001) suggesting a critical role of the newly formed intratubular Ang II on sodium reabsorption and blood pressure

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Conclusion