The blood pressure lowering effect of a
pea protein hydrolysate (PPH) that contained <3 kDa
peptides, isolated by membrane ultrafiltration from the
thermolysin digest of
pea protein isolate (PPI), was examined using different rat models of
hypertension as well as hypertensive human subjects. The PPH showed weak in vitro activities against
renin and
angiotensin converting enzyme (ACE) with inhibitory activities of 17 and 19%, respectively, at 1 mg/mL test concentration.
Oral administration of the PPH to spontaneously hypertensive rats (SHR) at doses of 100 and 200 mg/kg
body weight led to a lowering of hourly systolic blood pressure (SBP), with a maximum reduction of 19 mmHg at 4 h. In contrast, orally administered unhydrolyzed PPI had no blood pressure reducing effect in SHR, suggesting that
thermolysin hydrolysis may have been responsible for releasing bioactive
peptides from the native
protein.
Oral administration of the PPH to the Han:SPRD-cy rat (a model of
chronic kidney disease) over an 8-week period led to 29 and 25 mmHg reductions in SBP and diastolic blood pressure, respectively. The PPH-fed rats had lower plasma levels of
angiotensin II, the major vasopressor involved in development of
hypertension, but there was no effect on plasma activity or renal
mRNA levels of ACE. However, renal expression of
renin mRNA levels was reduced by approximately 50% in the PPH-fed rats, suggesting that reduced
renin may be responsible for the reduced levels of
angiotensin II. In a 3-week randomized double blind placebo-controlled crossover human intervention trial (7 volunteers), significant (p<0.05) reductions (over placebo) in SBP of 5 and 6 mmHg were obtained in the second and third weeks, respectively, for the PPH group. Therefore,
thermolysin derived bioactive
peptides from PPH reduced blood pressure in hypertensive rats and human subjects, likely via effects on the renal
angiotensin system.