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European Journal of Clinical Pharmacology

, Volume 14, Issue 3, pp 171–176 | Cite as

The effect of angiotensin II blockade by saralasin (1-Sar-8-Sla-angiotensin II) in normal man

  • H. Ibsen
  • A. M. Kappelgaard
  • M. Damkjær Nielsen
  • J. Giese
Originals

Summary

The effects of the angiotensin II analogue saralasin were investigated in 6 normal individuals. Blood pressure, plasma renin (PRC), plasma aldosterone (PAC) and plasma saralasin were measured before and during infusion of saralasin (0.54–5.4 nmol/kg/min) with the subjects supine. Plasma angiotensin II concentration (PA II) was measured before the infusion. In the sodium replete state, PA II averaged 11 pmol/1 (range 5 to 17). Saralasin infusion produced an increase in mean arterial pressure (MAP) and PAC, and a slight fall in PRC, which is consistent with an angiotensin II-like effect or a so-called agonistic effect. After sodium depletion, induced by hydrochlorothiazide 50–100 mg/day for 5 days, PA II was high −91 pmol/l on average (range 41 to 217). Angiotensin II blockade produced a fall in MAP in the supine position. The agonistic effect of saralasin on adrenal receptors during sodium depletion was less pronounced or absent. PRC increased sharply during the infusion. Infusion of saralasin at the rate of 5.4 nmol/kg/min produced a plasma saralasin concentration of about 220 nmol/l, i. e. in molar terms the plasma concentration of the analogue was 2000 to 10000 times higher than that of the endogenous octapeptide. The relationship between changes in MAP and basal PA II prior to infusion showed that saralasin exhibited a shift from agonistic to antagonistic properties on vascular receptors when pre-infusion PA II changed from approximately 20 to 40 pmol/l. A shift from agonistic to antagonistic effect on aldosterone secretion was not consistently seen. It is concluded that angiotensin II does not have a decisive role in the maintenance of normal blood pressure during normal sodium balance. However, after sodium depletion the renin-angiotensin system contributes to blood pressure control, even in the supine position. In addition to its antagonistic properties, saralasin possesses a weak agonistic effect on vascular, as well as on renal and adrenal receptors. This has to be taken into consideration when saralasin infusion is used to define “angiotensin II dependency” in patients with hypertension.

Key words

Angiotensin II angiotensin II antagonist aldosterone renin saralasin bloodpressure control 

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Copyright information

© Springer-Verlag 1978

Authors and Affiliations

  • H. Ibsen
    • 1
  • A. M. Kappelgaard
    • 1
  • M. Damkjær Nielsen
    • 1
  • J. Giese
    • 1
  1. 1.Department of Clinical PhysiologyGlostrup HospitalGlostrupDenmark

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