Characterization of the angiotensin II (AngII) model of hypertension for inter‐laboratory investigation±

Abstract

A recent report showed that in a well established model of salt-dependent hypertension—the AngII-induced model—arterial pressure (AP) did not increase in when AngII was given intravenously (iv) by osmotic minipumps and AP was measured by telemetry in rats on a normal salt diet (Hypertension 42: 798, 2003). To address this controversy we assessed the AP responses to AngII in rats on three levels of dietary salt (0.1%, 0.4% and 2.0% NaCl) in one laboratory, and determined the reproducibility of the model in four separate laboratories. AP was measured by telemetry for 7 control days and 14 days of AngII by osmotic minipump. Initial studies showed that minipumps were unreliable for iv AngII; therefore AngII was given subcutaneously (150 ng/kg/min). Control AP was similar between groups but the response to AngII was directly related to salt intake. By Day 14 of AngII AP increased 10 + 3 (n=6), 27 + 7 (n=6) and 44 + 9 (n=6) mmHg in 0.1%, 0.4% and 2.0% NaCl rats respectively in one laboratory. Moreover, the responses to AngII in rats consuming 0.4% and 2.0% NaCl diets were similar in 4 laboratories. By Day 14 of AngII AP increased 17 + 3 (n=27) and 33 + 4 mm Hg (n=26) for 0.4% and 2.0% NaCl rats respectively. We conclude that the AngII-induced model is salt-sensitive and is reproducible among different laboratories when AngII is infused subcutaneously by osmotic minipumps. NIH Grant HL 076312