His-Leu, an angiotensin I-derived peptide, does not affect haemodynamics in rats

Abstract

Introduction:: The dipeptide histidine-leucine (His-Leu) is formed in the process of converting angiotensin I into angiotensin II. Several studies show that short peptides containing His-Leu may produce significant haemodynamic effects; however, to the best of our knowledge, data on haemodynamic effects of His-Leu are not available in medical databases.

Materials and methods:: We evaluated acute haemodynamic effects of intravenous administration of either 0.9% NaCl (vehicle) or His-Leu at a dose of 3-15 mg/kg body weight in anaesthetized 15-16-week-old, male, normotensive Wistar Kyoto and spontaneously hypertensive rats. Chronic effects of treatment with either the vehicle or His-Leu at a dose of 15 mg/kg body weight given subcutaneously daily were determined during continuous telemetry recordings in freely moving rats.

Results:: In anaesthetized rats both the vehicle and His-Leu produced a mild and transient increase in blood pressure and no change in plasma renin activity. There was no significant difference in haemodynamics between the rats infused with the vehicle and the rats infused with His-Leu. In chronic studies, seven-day treatment with vehicle and with His-Leu did not affect arterial blood pressure in freely moving rats.

Conclusion:: His-Leu does not produce either acute or chronic changes in arterial blood pressure in normotensive and hypertensive rats.

Keywords: Blood pressure; angiotensin; dipeptides; histidine; leucine; renin–angiotensin system.

Figure 1.

Changes in mean arterial blood pressure (ΔMABP (mmHg)) and heart rate (ΔHR (beats/min)) after the intravenous infusion of either His-Leu (3, 6 or 15 mg/kg body weight) or 0.9% NaCl (vehicle) in anaesthetized normotensive Wistar Kyoto rats ((a) and (b)) and spontaneously hypertensive rats ((c) and (d)). *p < 0.05 vs. baseline.

Figure 2.

Changes in mean arterial blood pressure (ΔMABP (mmHg)) and heart rate (ΔHR (beats/min)) in freely moving normotensive Wistar Kyoto rats ((a) and (b)) and spontaneously hypertensive rats ((c) and (d)). Baseline: before treatment. Days 1–7: treatment with either 0.9 NaCl (vehicle) or His-Leu at a dose of 15 mg/kg body weight given subcutaneously daily. *p < 0.05 vs. baseline.