Activity of Des-Aspartyl1-Angiotensin II and Angiotensin II in Man
Why the study?
Does [des-Aspartyl1]-angiotensin II have different effects on blood pressure and aldosterone production compared to angiotensin II in normal male subjects?
Population
7 normal male subjects
Comparison
[des-Aspartyl1]-angiotensin II infusion vs Angiotensin II infusion
Design
Other
Follow-up
30 minutes per infusion
Authors
Discussion
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Member takes
Implication
Hypothesis-generating for distinct angiotensin receptor sites; leaves open targeted pathway studies before any clinical consideration.
Key Points
- To compare the vascular and adrenal steroidogenic activities of [des-Aspartyl(1)]-angiotensin II and angiotensin II in healthy men under normal and low dietary sodium conditions.
- Seven normal male subjects were evaluated during a 5-day normal sodium intake (urinary sodium 160.3 ± 5.0 meq/24 h) and restudied 1 month later after 5 days of low sodium intake (urinary sodium 10.5 ± 1.6 meq/24 h).
- Subjects received sequential 30-minute graded infusions of angiotensin II (2 to 6 pmol/kg per min) and [des-Asp]-angiotensin II (2 to 18 pmol/kg per min) on consecutive days during each dietary sodium phase.
- During normal sodium intake, [des-Asp]-A II (2 to 18 pmol/kg per min) increased mean blood pressure from 85.2 ± 3 to 95.3 ± 5 mm Hg and aldosterone from 5.2 ± 1.1 to 14.3 ± 1.9 ng/100 ml, whereas A II (2 to 6 pmol/kg per min) increased blood pressure from 83.3 ± 4 to 102.3 ± 4 mm Hg and aldosterone from 7.0 ± 2.2 to 26.8 ± 2.0 ng/100 ml.
- Under sodium deprivation, [des-Asp]-A II elevated blood pressure from 83.7 ± 3 to 86.7 ± 3 mm Hg and aldosterone from 34.4 ± 6.0 to 51.0 ± 8.2 ng/100 ml, while A II elevated blood pressure from 83.0 ± 3 to 96.0 ± 4 mm Hg and aldosterone from 42.0 ± 9.7 to 102.2 ± 15.4 ng/100 ml.
- At matched doses (2 and 6 pmol/kg per min) during normal sodium intake, [des-Asp]-A II exhibited 11% to 36% of the pressor potency and 15% to 30% of the steroidogenic potency of A II, with both peptides showing equal suppression of renin release.
Structured PICO
Does [des-Aspartyl1]-angiotensin II have different effects on blood pressure and aldosterone production compared to angiotensin II in normal male subjects?
P
Population
7 normal male subjects
I
Intervention
[des-Aspartyl1]-angiotensin II ([des-Asp]-A II) infusion (2 to 18 pmol/kg per min for 30 min)
C
Comparator
Angiotensin II (A II) infusion (2 to 6 pmol/kg per min for 30 min)
O
Outcome
Blood pressure and plasma aldosterone concentrationsurrogate
[des-Asp]-A II has biologic activity in humans but is less efficacious than A II in stimulating aldosterone production and increasing blood pressure, with differing dose-response curves suggesting potentially different receptor sites.
Cite This Study
Carey et al. (1978) studied this question.