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

Effect of paracetamol on gastric erosions induced by indomethacin in rats

Gastric mucosal injury induced by application of indomethacin, as a nonsteroidal anti inflammatory drug [NSAID], is a well- documented phenomenon. This study examined the effect of acetaminophen [paracetamol] on indomethacin. - induced gastric erosions. One hundred adult albino rats of both sexes. weighing 200-250 gm were divided into two main groups. including a group of 10 rats acts as a control. The first group was to study the effect of a single oral dose of indomethacin. paracetamol and both drugs on the gastric mucosa. and the second group was to study the effect of repeated administration of each drug and both drugs together. The animals were killed and the histopathological changes of the stomach were examined microscopically. Single therapeutic dose of indomethacin was found to induce multiple gastric erosions which these were more markced after repeated administration of the drug. Single dose or prolonged administration of paracetamol were followed by very minimal changes in the gastric mucosa. Simultaneous administration of both drugs was found to reduce the pathological lesions induced by indomethacin alone, whereas the pretreatment with paraceramol one hour before a single oral dose of ndomethacin did not affect its erosive activity. Post - treatment with paracetamol reduces the erosive effect of indomethacin either in a single dose or after repeated administration. The pathogenesis of gastric erosions and ulcers was believed to he due to prostaglandin inhibition. Indomethacin was known as a potent inhibitor of prostaglandin synthesis, whereas paracetamol is a very weak inhibitor of prostaglandin production. It is also found that paracetamol had a protective action against the erosive effect of indomethacin and this appears to be mediated by mucosat regeneration, probably resulting from increased production of mucosa growth factors. So, the use of paractamal as antipyretic and analgesic drug is recommended instead of indomethacin. or they are administrated simultaneously with or after indomethacin when there is a possibility of gastric mucosal injury, especially in prolonged treatment