Perindoprilat (S 9780) is an angiotensin-converting enzyme (ACE) inhibitor with an IC50 value ranging from 1.5 nM. Besides, Perindoprilat shows an affinity for bradykinin and angiotensin I with specific binding rates of 47% and 33%, respectively. Moreover, Perindoprilat has the potential for research of hypertension.
Angiotensin-converting enzyme (ACE) is a central component of the renin-angiotensin system (RAS). Besides, ACE controls blood pressure by regulating the volume of fluids in the body. What’s more, ACE converts the hormone angiotensin I to the active vasoconstrictor angiotensin II. Therefore, ACE indirectly increases blood pressure by causing blood vessels to constrict.
Perindoprilat shows activity on human mesangial cells.
Perindoprilat (40 µM; 3 days) decreases in macrophage-conditioned medium (MPCM)-stimulated fibronectin levels of 19.4 ± 0.6% (P < 0.001) and 21.7 ± 1.0% (P < 0.001) for secreted and cell-associated fibronectin levels, respectively in quiescent mesangial cells. Besides, Perindoprilat decreases MPCM-stimulated supernatant laminin protein levels by 23.2 ± 1.72%. Moreover, Perindoprilat (40 µM; 18 h) with MPCM doesn’t appear to decrease fibronectin protein synthesis and unchanged the fibronectin mRNA levels. Furthermore, Perindoprilat (18 h) significantly up-regulates the expression of bradykinin B2 receptor by 71 ± 30% (P = 0.032). Additionally, bradykinin B2 receptor antagonist HOE 140 (1 µM) reverses the perindoprilat-mediated reduction in mesangial cell fibronectin levels. In a word, Perindoprilat shows renoprotection in the context of macrophage-stimulated mesangial cell scarring.
Perindoprilat inhibits ACE in the plasma and tissues, thereby preventing the formation of angiotensin II. Besides, Perindoprilat significantly increases circulating bradykinin levels. Perindoprilat shows rapid metabolism, it can be detected in the plasma within 30 min of administration. Furthermore, Perindoprilat is weakly bound to plasma proteins, which reduces the potential for drug interactions. Moreover, perindoprilat has a half-life of 5 h.
In conclusion, Perindoprilat is a potent ACE inhibitor and has the potential for hypertension research.