The Brain Renin-Angiotensin System Contributes to the Hypertension in Mice Containing Both the Human Renin and Human Angiotensinogen Transgenes

• Published in: Circulation research 1998-11, Vol.83 (10), p.1047-1058
• Main Authors: Davisson, Robin L, Yang, Gongyu, Beltz, Terry G, Cassell, Martin D, Johnson, Alan Kim, Sigmund, Curt D
• Format: Article
• Language: English
• Subjects: Angiotensins - genetics; Angiotensins - metabolism; Animals; Antihypertensive Agents - pharmacology; Arginine Vasopressin - blood; Arginine Vasopressin - pharmacology; Arterial hypertension. Arterial hypotension; Biological and medical sciences; Blood and lymphatic vessels; Blood Pressure - drug effects; Blood Pressure - physiology; Brain Chemistry - physiology; Brain Stem - chemistry; Brain Stem - metabolism; Cardiology. Vascular system; Cerebellum - chemistry; Cerebellum - metabolism; Cerebral Cortex - chemistry; Cerebral Cortex - metabolism; Diencephalon - chemistry; Diencephalon - metabolism; Experimental diseases; Ganglionic Blockers - pharmacology; Gene Expression - physiology; Hexamethonium - pharmacology; Humans; Hypertension - metabolism; Injections, Intraventricular; Losartan - pharmacology; Medical sciences; Mice; Mice, Transgenic; Pulsatile Flow; Renin - genetics; Renin - metabolism; Renin-Angiotensin System - physiology; Space life sciences; Transgenes - physiology; Vasoconstrictor Agents - blood; Vasoconstrictor Agents - pharmacology
• ISSN: 0009-7330; 1524-4571
• DOI: 10.1161/01.res.83.10.1047

We have previously shown that mice transgenic for both the human renin and human angiotensinogen genes (RA+) exhibit appropriate tissue- and cell-specific expression of both transgenes, have 4-fold higher plasma angiotensin II (AII) levels, and are chronically hypertensive. However, the relative contribution of circulating and tissue-derived AII in causing hypertension in these animals is not known. We hypothesized that the brain renin-angiotensin system contributes to the elevated blood pressure in this model. To address this hypothesis, mean arterial pressure (MAP) and heart rate were measured in conscious, unrestrained mice after they were instrumented with intracerebroventricular cannulae and carotid arterial and jugular vein catheters. Intracerebroventricular administration of the selective AII type 1 (AT-1) receptor antagonist losartan (10 [micro sign]g, 1 [micro sign]L) caused a significantly greater peak fall in MAP in RA+ mice than in nontransgenic RA- controls (-29 +/- 4 versus -4 +/- 2 mm Hg, P0.05), whereas AVPX caused a significantly greater fall in MAP in RA+ compared with RA- mice (-24 +/- 2 versus -6 +/- 1, P