Effects of captopril and losartan on thermal and chemical induced pain in mice.
Angiotensin converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers antagonists (ARAs) are widely used compounds in various cardiovascular disorders. ACEIs, but not ARAs, inhibit the enzyme dipeptidyl carboxypeptidase which is involved in the conversion of angiotensin I to II and degradation of kinins like bradykinin and substance P. Bradykinin and substance P are potent mediators of inflammation and pain. Hence the study was undertaken to evaluate the effects of captopril (an ACEI) and losartan (an ARA-AT1 receptor antagonist) on thermal and chemical induced nocioception by employing hot plate and acetic acid induced writhing tests respectively in mice. Inbred albino mice weighing between 25-30 g were used and they were divided into two sets, each set containing 7 groups. Control groups received normal saline and the remaining six groups received three doses (0.5, 1 and 2 mg/kg) of captopril and three doses (0.5, 1 and 2 mg/kg) of losartan. Drugs were administered intraperitoneally fifteen minutes before placing the animal over the hot plate or 30 minutes before injecting 0.6% acetic acid. Both drugs dose dependently reduced the reaction time in hot plate method. In chemical induced writhing test, both the drugs reduced the latency of onset of writhing and in captopril pretreated groups, acetic acid induced sustained abdominal contraction without any intermittent relaxation. However, in losartan pretreated animals acetic acid just increased the number of writhings without sustained abdominal contraction. Thus, our study suggests that both drugs have hyperalgesic effects.
Rohit
Department of Pharmacology, Kasturba Medical College, Mangalore 575 001.
Rao
Chakradhar
C
Krishna
Gopala
G
D000804:Angiotensin II / Q000502:physiology; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D002216:Captopril / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006930:Hyperalgesia / Q000139:chemically induced*; D019808:Losartan / Q000494:pharmacology*; D008297:Male; D051379:Mice; D011930:Reaction Time / Q000187:drug effects
D047228:Angiotensin II Type 1 Receptor Blockers; D000806:Angiotensin-Converting Enzyme Inhibitors; D000804:Angiotensin II; D002216:Captopril; D019808:Losartan