Effect of perindopril [angiotensin converting enzyme inhibitor] on vasoconstrictor activity of hypertensive rats

In the present study we investigated the possibility that perindopril changes the post synaptic vasoconstrictor activity to a variety of vasoconstrictive agents. Perindopril [10 mg/kg/day] administrated orally to spontaneously hypertensive rat [SHR] for 7 days, significantly reduced the potency and the maximal vasopressor response to phenylephrine [40%] and the maximal response to serotonin [50%] compared with the responses from vehicle treated SHR. In contrast, perindopril had no significant effect on the pressor responses to KCl. Furthermore, an equipotent antihypertensive dose of hydralazine [5 mg/kg/day, per oral for 7 days] exerted no inhibitory effect on the pressor responses elicited by phenylephrine or KCl, but significantly reduced the maximal response to serotonin. The results suggest that 7-days perindopril administration reduced alpha adrenoceptor and serotonergic receptor-mediated vasoconstriction. However, perindopril did not reduce the vasoconstrictor responses induced by KCl, indicating that those pressor response that are due to depolarization are. in part, independent of angio-tensin-converting enzyme inhibition. This inhibition of vascular adrenoceptor and -serotonergic receptor pressor activity may underlie, in part, the long-term antihypertensive activity of perindopril in the spontaneously hypertensive rat