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. 1991 Jun;103(2):1585–1591. doi: 10.1111/j.1476-5381.1991.tb09831.x

Cardiac haemodynamic effects of the non-peptide, angiotensin II-receptor antagonist, DuP 753, in conscious Long Evans and Brattleboro rats.

P Batin 1, S M Gardiner 1, A M Compton 1, P A Kemp 1, T Bennett 1
PMCID: PMC1908375  PMID: 1884112

Abstract

1. In previous experiments in conscious, water-replete Long Evans and Brattleboro rats the non-peptide angiotensin II-receptor antagonist, DuP 753, caused only slight hypotension and peripheral (particularly renal) vasodilatations. However in water-deprived (i.e. renin-dependent) Brattleboro rats, DuP 753 caused marked hypotension and regional vasodilatations. The major objective of the present study was to determine if the hypotensive effects of DuP 753 under any of the experimental conditions studied previously were contributed to by negative effects on cardiac haemodynamics. 2. Male, Long Evans and Brattleboro rats were chronically instrumented with electromagnetic flow probes on the ascending aorta and with intravascular catheters. Data were collected by use of a microcomputer-based system that provided digitised print-out of instantaneous heart rate, mean arterial blood pressure, cardiac output, stroke volume, peak aortic flow, maximum positive slope of the aortic flow signal (+ dF/dtmax), total peripheral conductance and central venous pressure. 3. Incremental i.v. bolus doses (0.1-10 mg kg-1, at 15 min intervals) of DuP 753 were administered to water-replete Long Evans (n = 8) and Brattleboro (n = 8) rats, and to water-deprived (14 h) Brattleboro rats (n = 9) (the latter animals show marked activation of the renin-angiotensin system). In all groups, 15 min after the highest dose of DuP 753 had been given, a supramaximal dose of captopril (2 mg kg-1) was injected to determine if it had any additional effects. 4. In water-replete, Long Evans and Brattleboro rats, DuP 753 (0.1-1 mg kg-1) caused slight, transient hypotension, with rises in total peripheral conductance; increases in cardiac output, peak aortic flow, + dF/dtmax and stroke volume were inconsistent and central venous pressure did not change.(ABSTRACT TRUNCATED AT 250 WORDS)

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Selected References

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