Does Brain Natriuretic Peptide Have a Direct Renal Effect in Human Hypertensives?

Abstract

Abstract-Systemic infusion of brain natriuretic peptide (BNP) stimulates natriuresis and diuresis but has variable effects on the renal vasculature. In this study, we investigated whether BNP has any direct effects on the kidney in hypertensive patients. Three stepwise increasing doses of BNP (60, 120, and 180 pmol/min) or placebo were infused into the renal artery of 26 hypertensive patients. Renal blood flow was determined with the 133 Xenon washout technique. Before and after infusion of BNP, arterial and venous blood samples were taken for cGMP, renin, and creatinine concentration. Intra-arterial blood pressure and heart rate were monitored continuously. Intrarenal BNP infusion did not induce significant changes in renal blood flow despite increases in circulating levels of cGMP. The latter, however, was not associated with changes in the cGMP gradient across the kidney. In addition, we did not find any BNP-related changes in the secretion of active renin and in creatinine extraction. At the highest dose, heart rate increased after BNP infusion without a change in mean intra-arterial blood pressure. In conclusion, this study suggests that at least in hypertensive subjects, BNP has no direct intrarenal hemodynamic effects and that the rise in circulating cGMP without changes in net renal extraction of this second messenger is related to a primary extrarenal target of BNP. Key Words: natriuretic peptides Ⅲ vasodilation Ⅲ hypertension, renal Ⅲ human Ⅲ kidney Ⅲ hemodynamics Ⅲ vasoconstriction Ⅲ hormones S ystemic infusion of brain natriuretic peptide (BNP) stimulates natriuresis and diuresis 1-6 and inhibits plasma renin activity [1][2][3]7,8 but has variable effects on the renal vasculature. Although most but not all studies in healthy humans reported that BNP infusion increases glomerular filtration rate, 1,5-7 renal plasma flow has been found to decrease, 1,7 to increase, 5 or to remain unchanged. 3,8 Variations in the renovascular effects of BNP could be related to differences in BNP levels reached during the experiments, but it is equally possible that the renal changes are, in part, secondary to systemic effects. Indeed, BNP not only acts on the kidney but also affects blood pressure, heart rate, cardiac output, and systemic vascular resistance. 2,3,5,6,8,9 In those studies in which changes in renal plasma flow are reported, it is important to keep in mind that such alterations may simply be due to concurrent changes in cardiac output. If, for instance, renal fraction (that is, the proportion of cardiac output perfusing the kidneys) remains unaltered during systemic BNP infusion, it is unlikely that the peptide has exerted a direct effect on the renal vasculature. If, on the other hand, renal fraction increases, relative renal vasodilation must have occurred. In most studies, this has not been taken into account.Local administration of BNP in a regional vascular bed in amounts that will not have systemic effects allows for assessing whether BNP has any direct effects on certain parts of the circulation. Wi...

Diuretic pattern in adults with nocturnal polyuria: The possible contribution of blood pressure to the worsening of nocturnal polyuria

“…Moreover, there are previous reports referring to the possible contribution of natriuretic peptide to NP 10 . Regarding this issue, however, a more recent investigation reported that BNP had no direct intrarenal hemodynamic effects in hypertensive patients 30 . The present study also showed that BNP was not an independent determinant in increasing nocturnal diuresis or decreasing daytime diuresis.…”

Vascular and renal actions of brain natriuretic peptide in man: physiology and pharmacology

“…Infusion of BNP induced natriuresis also in patients with heart failure, but the natriuretic effect was impaired compared with healthy subjects and hypertensive patients [19,24,[49][50][51], most likely because of reduced responsiveness of the distal part of the nephron [19]. Surprisingly, infusion of high doses of BNP directly into the renal artery of patients with hypertension does not induce acute changes in renal blood flow [74]. Possibly, this lack of an acute renal vascular effect of BNP is caused by the simultaneous stimulation of vasodilatory and vasoconstrictive mechanisms, as a close relationship has been found between BNP and endothelin (ET-1) in the kidney [75].…”

Modulation of the natriuretic peptide system in heart failure: from bench to bedside?

“…Intriguingly, no additive effect on the renin-angiotensin-aldosterone system (RAAS) and sympathetic nervous system (SNS) (heart rate and plasma catecholamines) was seen at the infused doses (leading to low pathophysiological concentrations) [70,71]. In a study in mildly hypertensive subjects both peptides (given intravenously) suppressed the RAAS to a similar degree [74], whereas in another study intra-renal BNP infusion did not induce changes in renal blood flow, secretion of active renin or creatinine extraction [76].…”