Atrial natriuretic peptides and renin release

doi:10.1016/0002-9343(88)90214-8

The American Journal of Medicine

Volume 84, Issue 3, Supplement 1, 11 March 1988, Pages 112-118

https://doi.org/10.1016/0002-9343(88)90214-8 Get rights and content

Abstract

The relationship between endogenous plasma concentrations of atrial natriuretic peptide and renin was examined in resting normal subjects and patients with cardiac impairment. To test the hypothesis that atrial natriuretic peptide inhibits renin secretion, intravenous infusions of atrial natriuretic peptide were administered to normal volunteers, patients with end-stage renal failure, and conscious dogs in both sodium-replete and sodium-depleted states. Plasma atrial natriuretic peptide and renin were inversely related in normal subjects (r = −0.52, n = 140, p <0.001), but a weak positive association between these two variables was observed in patients with cardiac impairment (r = 0.32, n = 60, p <0.02). Low doses of both 26- and 28-amino-acid human atrial natriuretic peptide (2 pmol/kg/minute for two hours) given to sodium-replete normal subjects halved plasma renin compared with time-matched placebo values (19 ± 4 and 18 ± 3 versus 36 ± 8 μU/ml, p <0.001 for both). Incremental doses of synthetic atrial natriuretic peptide suppressed plasma renin below time-matched placebo values in both sodium-replete (maximal suppression 1.2 ± 0.4 versus 8.6 ± 1.4 μU/ml, p <0.001) and sodium-depleted (maximal suppression 18.9 ± 4.9 versus 51 ± 13 μU/ml, p <0.05) dogs. This effect was initially apparent at low doses of atrial natriuretic peptide (1 pmol/kg/minute), and renin suppression was maximal, in both states, with lesser doses of atrial natriuretic peptide than those at which maximal natriuresis was observed. Atrial natriuretic peptide administered to patients with end-stage renal failure (10 pmol/kg/minute for one hour) caused no change in plasma renin. These data confirm that atrial natriuretic peptide inhibits renin secretion in a dose-related manner and suggest that this action of the peptide is modified by both the baseline sodium status and renal function of the recipient.

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Cited by (42)

Current and future therapeutic perspective in chronic heart failure
2022, Pharmacological Research
Citation Excerpt :
The main biological effects of natriuretic peptides are diuresis and natriuresis, inhibition of secretion and production of neurohormonal factors (aldosterone, AII, endothelin, renin, vasopressin), decrease in blood pressure, and inhibition of cardiac and vascular remodeling [30]. Considering the positive effects determined by NPs, they probably are a compensatory mechanism to attenuate the deleterious RAAS-induced impact [33]. However, the increased levels of NPs are insufficient to balance the RAAS and SNS hyperactivation, probably for establishing several resistance mechanisms [9].
The incidence of heart failure is primarily flat or declining for a presumably reflecting better management of cardiovascular diseases, but that of heart failure with preserved ejection fraction (HFpEF) is probably increasing for the lack of an established effective treatment. Moreover, there is no specific pharmacological treatment for patients with heart failure with mildly reduced ejection fraction (HFmrEF) since no substantial prospective randomized clinical trial has been performed exclusively in such population. According to the recent 2021 European Society of Cardiology (ESC) guidelines, the triad composed of an Angiotensin Converting Enzyme inhibitor or Angiotensin Receptor-Neprilysin Inhibitor (ARNI), a beta-blocker, and a Mineralcorticoid Receptor Antagonist is the cornerstone therapy for all patients with heart failure with reduced ejection fraction (HFrEF) but a substantial gap exists for patients with HFpEF/HFmrEF. Despite the important role of the Renin-Angiotensin-Aldosterone System (RAAS) in heart failure pathophysiology, RAAS blockers were found ineffective for HFpEF patients. Indeed, even the new drug class of ARNI was found effective only in HFrEF patients. In this regard, a therapeutic alternative may be represented by drug stimulating the non-classic RAAS (ACE2 and A1–7) as well as other emerging drug classes (such as SGLT2 inhibitors). Reflecting on this global health burden and the gap in treatments among heart failure phenotypes, we summarize the leading players of heart failure pathophysiology, the available pharmacological treatments for each heart failure phenotype, and that in future development.
The historical evolution of knowledge of the involvement of neurohormonal systems in the pathophysiology and treatment of heart failure
2019, Revista Portuguesa de Cardiologia
Nos anos 1980 assistiu‐se a uma evolução profunda do conhecimento sobre a fisiopatologia da insuficiência cardíaca (IC): outrora considerada uma síndrome clínica de origem fundamentalmente estrutural, a IC começou a ser vista como a consequência de um desequilíbrio de forças hormonais opostas. Foi, de facto, nesta década que surgiram os estudos basilares sobre o impacto dos sistemas neuro‐hormonais na IC. E destes destacam‐se oito: quatro de natureza vasoconstritora e antinatriurética (o sistema nervoso simpático [SNS], o sistema da renina‐angiotensina‐aldosterona [SRAA], o sistema da vasopressina arginina e a endotelina) e quatro de natureza vasodilatadora e natriurética (o sistema das protaglandinas [PGs], do óxido nítrico [NO], o sistema dopaminérgico e o sistema dos péptidos natriuréticos [NPS]). Fortemente interligados entre si e com um sistema de regulação intrincado, estes sistemas funcionam habitualmente numa homeostasia delicada, cuja disrupção é sinal característico da IC. Nesta revisão é explorado o desenvolvimento histórico do conhecimento sobre o impacto destes sistemas neuro‐hormonais na IC desde os seus primeiros estudos até ao conhecimento atual. Para além disso, são também revisitadas as oportunidades terapêuticas que cada um deles apresenta, bem como as famílias de antagonistas neuro‐hormonais atualmente utilizadas na terapia da IC. Nesta última parte dá‐se especial destaque ao último fármaco aprovado para utilização em doentes com IC com fração de ejeção reduzida, o sacubitril/valsartan, que combina dois antagonistas e que por isso atua simultaneamente em dois sistemas neuro‐hormonais: o SRAA e o NPS.
Our knowledge of the pathophysiology of heart failure (HF) underwent profound changes during the 1980s. Once thought to be of exclusively structural origin, HF began to be seen as the consequence of hormonal imbalance. A number of seminal studies were published in that decade focusing on the impact of neurohormonal activation in HF. Presently, eight neurohormonal systems are known to have a key role in HF development: four stimulate vasoconstriction and sodium/water retention (the sympathetic nervous system, the renin‐angiotensin‐aldosterone system [RAAS], endothelin, and the vasopressin‐arginine system), while the other four stimulate vasodilation and natriuresis (the prostaglandin system, nitric oxide, the dopaminergic system, and the natriuretic peptide system [NPS]). These systems are strongly interconnected and are subject to intricate regulation, functioning together in a delicate homeostasis. Disruption of this homeostasis is characteristic of HF. This review explores the historical development of knowledge on the impact of the neurohormonal systems on HF pathophysiology, from the first studies to current understanding. In addition, the therapeutic potential of each of these systems is discussed, and currently used neurohormonal antagonists are characterized. Special emphasis is given to the latest drug approved for use in HF with reduced ejection fraction, sacubitril/valsartan. This drug combines two different molecules, acting on two different systems (RAAS and NPS) simultaneously.
The pathophysiological role of natriuretic peptide-RAAS cross talk in heart failure
2017, International Journal of Cardiology
Citation Excerpt :
ANP and BNP levels are positively related to cardiac filling pressures while they are inversely related to indices of left ventricular function. Furthermore, under normal condition, there is an inverse correlation between NPs concentrations and RAAS stimulation, but in HF this correlation is positive [44]. The positive correlation is probably a compensatory mechanism to attenuate the RAAS hyperactivation and to maintain the cardiovascular homeostasis.
Chronic Heart Failure (HF) is still a disease state characterized by elevated morbidity and mortality and represents an unresolved problem for its socio-economic impact. Besides many of the pathophysiological events leading to advanced HF have been widely disclosed in the past decades, the role of neuro-hormonal dysregulation accompanying HF has to be clearly assessed with the objective of better therapeutic approaches in treating such a disease.
In the present review article, alongside with a brief re-evaluation of general aspects of HF physiopathology, we summarize recent advances in the cross talk between renin-angiotensin-aldosterone system (RAAS) with natriuretic peptides (NPs) which have been shown to play a relevant role in the development of severe HF.
The role of RAAS-NPs interplay has been shown to be crucial in both hemodynamic and tissue remodeling associated to cardiomyocyte dysfunction, leading to advanced impairment of left ventricular performance.
On the basis of these results, the development of drugs resetting both RAAS and NPs system seems to be promising for a successful long term treatment of chronic HF.
Natriuretic peptides for treatment of congestive heart failure
1999, American Heart Journal
Twenty-four-hour pattern of atrial natriuretic peptide in heart transplantation: evidence for lack of circadian rhythm. Temporal inter-relationships with plasma renin activity, aldosterone and cortisol
1993, International Journal of Cardiology
We have investigated the circadian rhythm of plasma atrial natriuretic peptide in 13 stable output heart transplanted patients, all without evidence of histological rejection and cardiac impairment, following antirejection therapy with Cyclosporine, Azathioprine and Prednisone. The 24-h pattern of plasma renin activity, plasma aldosterone and plasma cortisol has been studied as well. All the investigated variables were assayed six times over the 24-h span. The circadian time-qualified data were analyzed by ANOVA and Cosinor method. The 24-h mean levels of atrial natriuretic peptide, plasma renin activity and plasma aldosterone are significantly increased, while the concentrations of plasma cortisol are reduced in the heart transplanted recipients. ANOVA detected a significant within-day variability of all these humoral variables only in healthy subjects. A statistically significant circadian rhythm was validated by Cosinor procedure for all the investigated molecules in healthy subjects but not in heart transplanted patients. In our opinion, the increase of atrial natriuretic peptide is a counterregulatory mechanism aimed to compensate the cyclosporine-mediated activation of the renin-angiotensin-aldosterone system. The disappearance of the plasma renin activity, aldosterone and atrial natriuretic peptide circadian rhythm can be ascribed to the constant activation of the renin-angiotensin-aldosterone system. The hypocortisolism is due, in our opinion, both to glucocorticoid therapy and increase of plasma ANP concentration.
Extra-natriuretic effects of atrial peptide in humans
1993, Kidney International
Extra-natriuretic effects of atrial peptide in humans. To evaluate extra-natriuretic effects of atrial natriuretic peptide (ANP), plasma ANP (pANP) levels were assessed in seven healthy men on low-sodium diet (80 mEq NaCl/day), in basal conditions and during stepwise infusion of human ANP (2, 4, 8 and 16 ng/min/kg). To determine the individual physiological (PHY) pANP level, we measured pANP in the same subjects after a high-salt diet (400 mEq NaCl/day), that is, in a physiological stimulation of ANP. We then compared the effects of the PHY levels of ANP to the effects of pharmacological (PHA) pANP levels. Neither PHY nor PHA pANP levels modified creatinine clearance or blood pressure. The progressive rise in pANP levels was associated with increases in urinary excretion of Na⁺, K⁺ and urea. ANP alone respectively accounted for 41%, 30% and 92% of the increase in natriuresis, kaliuresis and urea excretion that occurred after changing salt intake from 80 to 400 mEq/day. Pharmacological ANP levels raised C_H₂O and reduced U_Osm. Interestingly, PHA levels were associated with significant decrease in serum K⁺ (from 4.5 ± .1 to 4.0 ± .1 mEq/liter) and plasma urea (from 31.9 ± 5 to 24.2 ± 4 mg/dl). The mean cumulative urinary potassium and urea losses corresponded to the theoretical body losses of potassium and urea; moreover, the individual cumulative urinary losses of potassium and urea significantly correlated with the corresponding decrement in their plasma levels. In conclusion, ANP has both physiological and pharmacological significance in the control of potassium and urea metabolism by decreasing plasma levels of K⁺ and urea through effects on the renal excretory function.

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^a: Dr. A. Mark Richards is a New Zealand MRC-Wellcome Overseas Research Fellow. Atrial peptides were made available by Merck Sharp & Dohme and Pfizer.

View full text

Atrial natriuretic peptides and renin release

Abstract

Lancet

Clin Chim Acta

Lancet

Lancet

Role of atrial natriuretic factor in renin release

Endocrinology

Effects of synthetic atrial natriuretic factor on renal function and renin release

Am J Physiol

A comparison of synthetic rat and human atrial natriuretic factor in conscious dogs

Hypertension

Effect of chronic infusion of synthetic atrial natriuretic factor (ANF 8-33) in conscious two-kidney, one-clip hypertensive rats

Effects of alpha-human atrial natriuretic peptide in essential hypertension

Hypertension

Atrial natriuretic peptide: evidence of action as a natriuretic hormone at physiological plasma concentrations in man

Clin Sci