Hemodynamic Effects of the Nitric Oxide Donor DETA/NO in Mice

Abstract

(Z)‐1‐[N‐(2‐aminoethyl)‐N‐(2‐ammonioethyl)amino]diazen‐1‐ium‐1,2‐diolate (DETA/NO) is a recently synthesized member of NO‐releasing, polyamine zwitterions, the so‐called NONOates, that spontaneously liberate NO in aqueous solutions. The aim of this study was to determine the hemodynamic effects of DETA/NO in normotensive and hypertensive mice. Male Swiss Outbred mice were implanted with TA11PA‐C20 blood pressure devices (Data Sciences International, USA). After recovery (7–10 days), blood pressure was monitored for 10 days while mice were receiving saline (0.1 ml/20 g/day, s.c.). Mice were then treated every four hours for 1 day with either DETA/NO 60 mg/kg i.p. or the inactive metabolite, diethylenetriamine 38 mg/kg (molar equivalent) i.p. After a 2 week wash‐out period, mice were treated with adrenocorticotrophic hormone (ACTH: 500 µg/kg/day, s.c.) for 10 days and re‐challenged with DETA/NO or diethylenetriamine. Results were expressed as mean ± SEM. After 10 days of saline treatment, baseline systolic and diastolic blood pressure (BP) were similar for animals subsequently receiving DETA/NO or the amine (123 ± 1/95 ± 3 and 124 ± 1/92 ± 0.2 mmHg) respectively. DETA/NO induced a profound fall in BP [Systolic: 74 ± 4 mmHg (− 40 ± 3%); Diastolic: 46 ± 4 mmHg (− 52 ± 4%)] and an increase in heart rate [729 ± 33 bpm (32 ± 2%)] within the first 80 minutes. Diethylenetriamine had no effect. ACTH treatment increased BP in both groups (137 ± 16/108 ± 12 and 161 ± 1/142 ± 1 mmHg) respectively. DETA/NO induced a profound fall in blood pressure [Systolic: 92 ± 11 mmHg (− 32 ± 7%); Diastolic: 68 ± 10 mmHg (− 35 ± 10%)] and an increase in heart rate [613 ± 36 bpm (18 ± 6%)] within the first 80 minutes. Again diethylenetriamine had no significant effect. There was no significant effect on body weight with any treatment. Thus DETA/NO has potent blood pressure lowering effects in both normotensive and hypertensive mice.