|
EFFECTS OF CHRONIC INDOMETHACIN TREATMENT AND
SUBSEQUENT DISCONTINUATION ON VASCULAR REACTIVITY IN RATS
Ozolua, R.I and Ezeudemba, I.
Department of Pharmacology &
Toxicology, Faculty of Pharmacy, University of Benin,
P.M.B 1154, Benin City 300001,
Nigeria
ABSTRACT
Idomethacin and other
non-steroidal anti-inflammatory drugs (NSAIDs) have been shown to blunt
blood pressure reduction by antihypertensive drugs but the nature of
vascular responses following chronic use had not been reported. We
therefore designed the present study to investigate the influence of 28
days of oral administration of 0.7 mg/kg/day and subsequent 14days of
discontinuation on aortic ring responses to some vocative agents. The
aortic ring were exposed to cumulative organ bath concentrations of
phenyleprine (PE) and potassium chloride (KCI). The rings were also
precontracted with either PE or KCI and then exposed to cumulative
concentrations of acetylcholine (Ach) and sodium nitroprusside (SNP).
Results showed that 28 days of idomethacin treatment significantly (p<
0.001) increased maximal contractile responses to PE but not to KCI.
Relaxant effects of Ach and SNP in PE- precontracted rings were not
significantly affected by chronic drug administration or subsequent
attenuation of relaxant responses to ACh and SNP (p<0.05 and p<0.0001
respectively) in rings which were precontracted with KCI. The
difference between the responses to PE and KCI may be due to their
different mechanism of induction of vascular contractility. The study
shows that chronic indomethacin administration and subsequent
discontinuation could affect vascular reactivity with implications for
antihypertensive therapy.
KEYWORDS:
Chronic indomehacin, discontinuation, aortic rings, contraction,
relacation. |
