## 3 Peptides with Antihypertensive Activity
The other sequences of ACE inhibitors identified in some Spanish cheeses are given in Table 3.  
Sequences of caseins were also the sources of other ACE-inhibiting peptides that were identified in cheeses: RPKHPIKHQ (source: \(\alpha\)s\({}_{1}\)-casein; Cheddar and Gouda; IC\({}_{50}\) = n.d. and 13.4 \(\upmu\)M, respectively), RPKHPIKHOGLPQ (source: \(\alpha\)s\({}_{1}\)-casein; Gouda; IC\({}_{50}\) = n.d.), YFPFPGPIP (source: \(\beta\)-casein; Gouda; IC\({}_{50}\) = 14.8 \(\upmu\)M), MPFPKYPVQPP (source: \(\beta\)-casein; Gouda; IC\({}_{50}\) = n.d.), RPKHPIK, RPKHPI, FVAPFPEVFGK (source: \(\alpha\)s\({}_{1}\)-casein, Cheddar; IC\({}_{50}\) = n.d.), YQEPVLGPVRGPFPIIV (source: \(\beta\)-casein; Cheddar; IC\({}_{50}\) = n.d.), RPKHPIKHOGLPQEV, RPKHPIKHOGLPQEVLEN, LLR, EVLNENLLRF (source: \(\alpha\)s\({}_{1}\)-casein, Fresco; IC\({}_{50}\) = n.d.), FVAPFPEVFGK, YQEPVLGPVRGPFPI, YQEPVLGPVRGPFPIIV (source: \(\beta\)-casein; Fresco; IC\({}_{50}\) = n.d.) [30]. [PERSON] et al. [38] isolated two peptides (LQP and MAP) from Danish skimmed milk cheese. LQP was originally known as ACE inhibitor identified in \(\alpha\)-zein hydrolyzed with thermolysin. MAP sequence was identified in \(\beta\)-casein and exhibited ACE inhibition (IC\({}_{50}\) = 0.8 \(\upmu\)M) and antihypertensive effect in SHR. Significant hypotensive effect of MAP tripeptide was observed at 8 h since oral administration (\(-\)17.0 mm Hg; dose 3 mg \(\times\) kg\({}^{-1}\) body weight) [38]. The potential of cheeses as diet components that may affect the reduction of blood pressure is also in the focus of interest of the scientists aiming at meta-analyses [39]. [PERSON] et al. [39] carried out a cross-sectional study to analyze the impact of the consumption of Gamalost cheese (a traditional Norwegian cheese) on the reduction of the risk of hypertension development. Based on data obtained from the questionnaires of 168 participants, the average intake of Gamalost servings per week was 2 and the average value of systolic and diastolic blood pressures was 128 and 78 mmHg, respectively. \begin{table}
\begin{tabular}{c c c c c} \hline \hline
**Cheese** & **Peptide** & **IC\({}_{50}\) (\(\upmu\)M)** & **Precursor** & **Reference** \\ \hline \hline Manchego, Roncal, Idiazabal, Cabrales, goat & DKIHPF & 113.1 & & \\ \cline{2-5}  & DKIHPF & 2419.4 & \(\upbeta\)-casein & [36] \\ \hline Goat & VRGP & 120.9 & & \\ \hline \hline Manchego, Roncal, Idiazabal, Goat & PFP & 144.4 & & \\ \hline \hline Roncal & PKHP & 709.1 & \(\alpha\)s\({}_{1}\)-casein & \\ \hline \hline \end{tabular}
\end{table} 
Table 3: ACE inhibitors identified in Spanish cheeses. Adapted by permission from [PERSON], European Food Research and Technology [36], 2006. The increase of Gamalost servings reduced the systolic blood pressure by 0.72 mm Hg. Moreover, it was concluded that blood pressure reduction related to Gamalost consumption was associated with the presence of ACE inhibitory peptides [39]. [PERSON] et al. [40] investigated the antihypertensive effect resulting from the consumption of Grana Padano cheese and observed that supplementation of Grana Padano cheese at a dose 30 g per day significantly lowered the systolic and diastolic blood pressure in mild-hypertensive subjects (~3.5 and~2.4 mm Hg, respectively) [40]. One of the meta-analyses concerned studies evaluating the association of CVD, coronary heart disease (CHD), and stroke with high vs. low cheese consumption. This analysis revealed that high cheese consumption lowered the relative risk for: total CVD (RR 0.90; 7; 8076), CHD (RR 0.86; 8; 7631), and stroke (RR 0.90; 7; 10,449). Respective numbers in the brackets represent: relative risk, number of studies, and number of documented events provided. Finally, the results indicated a nonlinear relationship between cheese consumption and decreasing risks of CVD, CHD, and stroke. Consumption of approximately 40 g of cheese per day ensured the best results in reducing the risks of dysfunctions related to hypertension [41].