Renal and hormonal responses to direct renin inhibition with aliskiren in healthy humans.

Détails

ID Serval
serval:BIB_301EDEB338B9
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Renal and hormonal responses to direct renin inhibition with aliskiren in healthy humans.
Périodique
Circulation
Auteur(s)
Fisher N.D., Jan Danser A.H., Nussberger J., Dole W.P., Hollenberg N.K.
ISSN
1524-4539[electronic]
Statut éditorial
Publié
Date de publication
2008
Volume
117
Numéro
25
Pages
3199-3205
Langue
anglais
Résumé
BACKGROUND: Pharmacological interruption of the renin-angiotensin system focuses on optimization of blockade. As a measure of intrarenal renin activity, we have examined renal plasma flow (RPF) responses in a standardized protocol. Compared with responses with angiotensin-converting enzyme inhibition (rise in RPF approximately 95 mL x min(-1) x 1.73 m(-2)), greater renal vasodilation with angiotensin receptor blockers (approximately 145 mL x min(-1) x 1.73 m(-2)) suggested more effective blockade. We predicted that blockade with the direct oral renin inhibitor aliskiren would produce renal vascular responses exceeding those induced by angiotensin-converting enzyme inhibitors and angiotensin receptor blockers. METHODS AND RESULTS: Twenty healthy normotensive subjects were studied on a low-sodium (10 mmol/d) diet, receiving separate escalating doses of aliskiren. Six additional subjects received captopril 25 mg as a low-sodium comparison and also received aliskiren on a high-sodium (200 mmol/d) diet. RPF was measured by clearance of para-aminohippurate. Aliskiren induced a remarkable dose-related renal vasodilation in low-sodium balance. The RPF response was maximal at the 600-mg dose (197+/-27 mL x min(-1) x 1.73 m(-2)) and exceeded responses to captopril (92+/-20 mL x min(-1) x 1.73 m(-2); P<0.01). Furthermore, significant residual vasodilation was observed 48 hours after each dose (P<0.01). The RPF response on a high-sodium diet was also higher than expected (47+/-17 mL x min(-1) x 1.73 m(-2)). Plasma renin activity and angiotensin levels were reduced in a dose-related manner. As another functional index of the effect of aliskiren, we found significant natriuresis on both diets. CONCLUSIONS: Renal vasodilation in healthy people with the potent renin inhibitor aliskiren exceeded responses seen previously with angiotensin-converting enzyme inhibitors and angiotensin receptor blockers. The effects were longer lasting and were associated with significant natriuresis. These results indicate that aliskiren may provide more complete and thus more effective blockade of the renin-angiotensin system.
Mots-clé
Administration, Oral, Adult, Amides, Angiotensin I, Angiotensin II, Antihypertensive Agents, Blood Pressure, Captopril, Diet, Dose-Response Relationship, Drug, Female, Fumarates, Glomerular Filtration Rate, Humans, Male, Middle Aged, Natriuresis, Predictive Value of Tests, Reference Values, Renal Circulation, Renal Plasma Flow, Renin, Sodium, Sodium, Dietary, Vasodilation
Pubmed
Web of science
Open Access
Oui
Création de la notice
02/04/2009 14:57
Dernière modification de la notice
20/08/2019 13:14
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