Angiotensin-Converting Enzyme (ACE)-inhibitors are treatment of choice in hypertensive patients. In this study we assessed the ACE-inhibitory activity of the natural dipeptide isoleucine-tryptophan (IW) and its influence on cardiac remodelling and coronary flow reserve.

Spontaneously hypertensive rats (SHR) were fed with food pellets containing Captopril (CA 68 mg/kg/day), IW (20 mg/kg/day) or none (control) for 14 weeks. Systolic blood pressure was measured via tail cuff method. Cardiac function and myocardial hypertrophy was assessed using in vivo echo and ex vivo isolated heart perfusion (Langendorff preparation) at end of study. Cardiac fibrosis was quantified using histological evaluation after Sirius red staining.

Both, CA and IW, significantly decreased systolic blood pressure by 55±8 and 44±5 mmHg, respectively, versus control. Cardiac echo revealed no differences in fractional myocardial shortening, but calculated left ventricular mass and heart weight were significantly lowered in CA and IW. Coronary flow reserve was significantly elevated in CA and IW versus placebo.

In conclusion, IW is a potent ACE-inhibitor in vivo with a similar antihypertensive potential as Captopril. The hypertensive effect is parallel by cardiac remodelling.