title: Intranasal angiotensin II in humans reduces blood pressure when angiotensin II type 1 receptors are blocked.
abstract: Intranasal administration of angiotensin II (ANGII) affects blood pressure in a mode different from intravenously administered ANGII via a direct access to the brain bypassing the blood-brain barrier. This clinical study investigated blood pressure regulation after intranasal ANGII administration in healthy humans, whereas systemic, blood-mediated effects of ANGII were specifically blocked. In a balanced crossover design, men (n=8) and women (n=8) were intranasally administered ANGII (400 μg) or placebo after ANGII type 1 receptors had been blocked by pretreatment with valsartan (80 mg; 12 and 6 hours before intranasal administration). Plasma levels of ANGII, aldosterone, renin, vasopressin, and norepinephrine were measured; blood pressure and heart rate were recorded continuously. Intranasal ANGII acutely decreased blood pressure without altering the heart rate. Plasma levels of vasopressin and norepinephrine remained unaffected. Plasma ANGII levels were increased throughout the recording period. Aldosterone levels increased despite the peripheral ANGII type 1 receptor blockade, indicating an aldosterone escape phenomenon. In conclusion, intranasal ANGII reduces blood pressure in the presence of selective ANGII type 1 receptor blockade. Intranasal ANGII administration represents a useful approach for unraveling the role of this peptide in blood pressure regulation in humans.
authors.affiliation: Medizinische Klinik I, Universität zu Lübeck, Ratzeburger Allee 160, 23538 Lübeck, Germany. inge.derad@uksh.de.
authors.forename: Inge
authors.initials: I
authors.lastname: Derad
authors.forename: Friedhelm
authors.initials: F
authors.lastname: Sayk
authors.forename: Hendrik
authors.initials: H
authors.lastname: Lehnert
authors.forename: Lisa
authors.initials: L
authors.lastname: Marshall
authors.forename: Jan
authors.initials: J
authors.lastname: Born
authors.forename: Martin
authors.initials: M
authors.lastname: Nitschke
mesh_terms: D000281:Administration, Intranasal; D000328:Adult; D000450:Aldosterone / Q000097:blood; D000804:Angiotensin II / Q000008:administration & dosage* / Q000494:pharmacology*; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects* / Q000502:physiology; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005260:Female; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D008297:Male; D044140:Receptor, Angiotensin, Type 1 / Q000187:drug effects*; D012084:Renin-Angiotensin System / Q000187:drug effects / Q000502:physiology; D013777:Tetrazoles / Q000494:pharmacology; D014633:Valine / Q000031:analogs & derivatives / Q000494:pharmacology; D000068756:Valsartan
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D044140:Receptor, Angiotensin, Type 1; D013777:Tetrazoles; D000804:Angiotensin II; D000450:Aldosterone; D000068756:Valsartan; D014633:Valine; D006854:Hydrocortisone
keywords: administration, intranasal; aldosterone; angiotensin II; blood pressure; central nervous system