Hemodynamic effects of the nitric oxide donor DETA/NO in mice.
(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 microg/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.
Schyvens
Chris G
CG
High Blood Pressure Research Unit, John Curtin School of Medical Research, The Australian National University, Canberra, Australia. chris.schyvens@anu.edu.au
Cowden
William B
WB
Zhang
Yi
Y
McKenzie
Katja U S
KU
Whitworth
Judith A
JA
D000324:Adrenocorticotropic Hormone / Q000494:pharmacology; D000818:Animals; D021461:Animals, Outbred Strains; D001794:Blood Pressure / Q000187:drug effects*; D006973:Hypertension / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D051379:Mice; D020030:Nitric Oxide Donors / Q000494:pharmacology*; D012965:Sodium Chloride / Q000494:pharmacology; D014226:Triazenes / Q000494:pharmacology*
C105351:1-hydroxy-2-oxo-3,3-bis(2-aminoethyl)-1-triazene; D020030:Nitric Oxide Donors; D014226:Triazenes; D012965:Sodium Chloride; D000324:Adrenocorticotropic Hormone