Role of the intrarenal renin-angiotensin system in the control of renal function.

Levens, Nigel; Peach, Michael J.; Carey, Robert M.

doi:10.1161/01.res.48.2.157

Cited by 178 publications

(58 citation statements)

References 72 publications

(73 reference statements)

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“…Since this would more than compensate for the hypotensive effect that resulted from removal of A II from plasma, blood pressure would rise above the control level. This explanation supports the concept of intrarenal production of A II as one component of an intrarenal renin-angiotensin system (Levens, Peach & Carey, 1981;Mendelsohn, 1982 (Peach, 1977 (Freeman, Davis & Lohmeier, 1975;Taub, Caldicott & Hollenberg, 1977;Caldicott, Taub, Margulies & Hollenberg, 1981). Other investigators however have reported that in the dog, A II is a more potent renal vasconstrictor than A III and demonstrated that this was not due to differential release of prostaglandins (Satoh, Itsukaichi, Ohyama & Hayashi, 1981).…”

Section: Discussionsupporting

confidence: 61%

Reversal by angiotensins II and III of the effects of converting enzyme inhibition on renal electrolyte excretion in rats.

Harris¹,

Munro²

1984

The Journal of Physiology

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SUMMARY1. Experiments were carried out in anaesthetized rats to compare the abilities of angiotensin II (A II) and angiotensin III (A III) to reverse the effects of angiotensin converting enzyme inhibition (Teprotide) on salt and water excretion.2. In rats infused with Teprotide, significant increases in urine flow and sodium excretion were observed and arterial blood pressure decreased. Addition of A II (10 pmol min-) to the Teprotide infusion reduced renal excretion of sodium and water to control values and excretion of potassium to below control. Blood pressure increased to a value significantly higher than that during the control period.3. In a separate group of rats the natriuretic and diuretic effects of Teprotide were reversed by a similar dose ofA III (10 pmol min-'). A primarily angiotensin-mediated action is indicated for the renal effects of Teprotide.4. Although angiotensins II and III appeared to be equipotent in their abilities to reverse the renal responses to Teprotide, A II caused an increase in arterial blood pressure that was not seen with A III. In a third group of rats A II (10 pmol min-) was added to the Teprotide infusion and an aortic snare located between the renal arteries was tightened to prevent any increase in left renal perfusion pressure. During this period the rate of sodium excretion from the left kidney was significantly lower than from the right kidney.5. It is concluded that in the absence of any accompanying 'pressure natriuresis' A II is more potent than A III in its ability to reverse the natriuretic action of Teprotide. The elevation of blood pressure to above control values by a dose of A II only just sufficient to reverse the Teprotide-induced natriuresis suggests that the concentration of angiotensin in the kidney is higher than in plasma and supports the concept of an intrarenal renin-angiotensin system. 6. In the rat both A II and A III may affect renal salt and water excretion by a combination of mechanisms involving glomerular, vascular and tubular receptors. The possibility is raised that differential effects of the active angiotensins on these mechanisms may participate in the regulation of sodium excretion.

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Section: Discussionsupporting

confidence: 61%

Reversal by angiotensins II and III of the effects of converting enzyme inhibition on renal electrolyte excretion in rats.

Harris¹,

Munro²

1984

The Journal of Physiology

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“…For example, increased renal prostaglandins preserve renal blood flow when cardiac output is low ( 16). There is increasing evidence that the kidney also contains a local RAS that may operate independently of the circulating RAS (17)(18)(19)(20)(21). The expressions of renin and angiotensinogen genes in the kidney have been demonstrated (20,22).…”

Section: Introductionmentioning

confidence: 99%

Evidence for tissue-specific activation of renal angiotensinogen mRNA expression in chronic stable experimental heart failure.

Schunkert¹,

Ingelfinger²,

Hirsch³

et al. 1992

J. Clin. Invest.

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The intrarenal renin-angiotension system (RAS) may contribute to the pathophysiology of heart failure by the generation of angiotensin II at local sites within the kidneys. Angiotensin II may directly influence renal hemodynamics, glomerular contractility, and tubular sodium reabsorption, thereby promoting sodium and fluid retention in this syndrome. In the present study, we examined components of the circulating RAS as well as the intrarenal expressions of renin and angiotensinogen mRNA in rats with stable compensated heart failure (HF) 12 wk after experimental myocardial infarction. Renal angiotensinogen mRNA level in vehicle-treated HF rats increased 47%, as compared with sham control rats (P = 0.001). The increase in angiotensinogen mRNA levels was more pronounced in animals with medium (46%, P < 0.05) and large (66%, P < 0.05) infarcts than in those with small infarcts (31%, P = NS). There were no differences in liver angiotensinogen mRNA, circulating angiotensinogen, angiotensin II, plasma renin concentration (PRC), kidney renin content (KRC), and renal renin mRNA level between sham and HFv. In addition, in a separate group of rats with heart failure, we demonstrated that renal angiotensin II concentration increased twofold (P < 0.05) as compared with that of age-matched sham operated controls. A parallel group of heart failure rats (HFe, n = 11) was treated with enalapril (25 mg/kg per d) in drinking water for 6 wk before these measurements. Blood pressure decreased significantly during treatment (91 vs. 103 mm Hg, P < 0.05). Enalapril treatment in HF rats increased renin mRNA level (2.5-fold, P < 0.005), KRC (5.6-fold, P = 0.005), and PRC (15.5-fold, P < 0.005). The increase in renal angiotensinogen mRNA level observed in HFv rats was markedly attenuated in enalapril treated HF rats (P < 0.001), suggesting a positive feedback of angiotensin II on renal angiotensinogen synthesis. These findings demonstrate an activation of intrarenal RAS, but no changes in the circulating counterpart in this model of experimental heart failure, and

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“…On the other hand, we observed a continuous activation of the RAAS by long-term inhibition of ANP, and angiotensin II causes vasoconstriction of the efferent arteriole as well as an increase in sodium reabsorption in proximal tubules. 26,27 Since the renal functions changed in proportion to the RAAS, the activated RAAS may play a part in the decreases in urinary water and sodium excretion, GFR and RPF in this study.…”

Section: Changes In Renal Functionsmentioning

confidence: 73%

Short-Term and Long-Term Inhibition of Endogenous Atrial Natriuretic Peptide in Dogs With Early-Stage Heart Failure

et al. 1998

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n congestive heart failure, neurohormonal factors such as the renin-angiotensin-aldosterone system (RAAS) and the sympathetic nervous system are activated, and the RAAS activation may lead to deterioration of heart failure (HF) due to the vasoconstrictive and volume-retaining effects. 1 Atrial natriuretic peptide (ANP) demonstrates increased secretion in proportion to the severity of HF, and may act to counterbalance the adverse effects of the RAAS through its direct vasodilatory action, inhibition of the excessive release of renin and aldosterone, and by its direct diuretic and natriuretic effects. [2][3][4] As reported in the Study of Left Ventricular Dysfunction (SOLVD), early-stage HF is characterized by an increase in circulating ANP without activation of the RAAS or body fluid retention. 5 Considering these hormonal profiles and the body fluid balance, ANP may be one of the principal factors inhibiting the activation of the RAAS and body fluid retention in early-stage HF. However, in advanced HF the intracardiac pressure increases, volume overload develops, and the RAAS activates in spite of the fact that the plasma ANP level remains elevated above basal values. Elevated plasma ANP in advanced HF may not be as effective as expected. In addition, the responsiveness to exogenous ANP decreases in renin suppression or renal excretion in advanced HF. 6 Thus the decreased responsiveness to endogenous ANP may play a part in the pathogenesis of vasoconstriction, activation of the RAAS and body fluid retention in HF. However, it has not been demonstrated experimentally whether hyporesponsiveness to ANP is directly related to the progression of HF.We and others have attempted to clarify the role of endogenous ANP in HF through short-term inhibition of ANP activity using an ANP receptor antagonist, HS-142-1. 4,[7][8][9][10][11] However, the influence of long-term inhibition of endogenous ANP activity by an ANP receptor antagonist in established HF, in which ANP has previously exerted an effect, has not been determined. We assumed that longterm inhibition of endogenous ANP activity in early-stage HF provokes the progression to advanced HF. It is important to examine how long-term inhibition of endogenous ANP affects cardiorenal and neurohormonal factors in early-stage HF in order to clarify the exact role of ANP in the progression from early-stage to advanced HF.The objective of the present study is to clarify whether endogenous ANP inhibits the deterioration of early-stage HF by investigating the effects of long-term suppression of endogenous ANP activity by HS-142-1 in dogs with earlystage HF. Furthermore, since it is expected that the longterm inhibition of endogenous ANP will cause the activation of various substances that affect vascular tone, hormonal secretion and renal functions, we compared the differences in the effects of short-term and long-term inhibition, and determined the direct and indirect influences of the suppression of endogenous ANP in early-stage HF. Short-Term and Long-Term Inhibition of Endoge...

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Role of the intrarenal renin-angiotensin system in the control of renal function.

Cited by 178 publications

References 72 publications

Reversal by angiotensins II and III of the effects of converting enzyme inhibition on renal electrolyte excretion in rats.

Reversal by angiotensins II and III of the effects of converting enzyme inhibition on renal electrolyte excretion in rats.

Evidence for tissue-specific activation of renal angiotensinogen mRNA expression in chronic stable experimental heart failure.

Short-Term and Long-Term Inhibition of Endogenous Atrial Natriuretic Peptide in Dogs With Early-Stage Heart Failure

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