Lecturer I, University of Lagos
Losartan-inuced GI motility changes studied to determine its role in reported GI disorder in users.
I am an early career academic and researcher in the field of Explorative Pharmacology and Toxicology at the University of Lagos Nigeria. I am actively involved in innovative research geared towards improvement and maintenance of health. My research team and I apply various in-silico, in-vivo, in-vitro and ex-vivo research methodologies to demonstrate yet to be explored aspects of the pharmacology and toxicology of various xenobiotics especially drugs and medicinal plants. This we do with the view to discover ways to optimize their therapeutic benefits. Drug-induced diarrhoea is a relatively frequent adverse effect. It is said to account for about seven percent of reported adverse reactions to drugs. Of the many drugs used in clinical practise, more than seven hundred drugs belonging to various therapeutic classifications have been reported to induce diarrhoea. Many more have been implicated in gastrointestinal disorders of various other kinds. It is accepted in some quarters that drug history taking during clinical consultations is essential for identification and proper diagnosis of diarrhoea and other gastrointestinal disorders that are drug induced. This is necessary to avoid needless time and money consuming diagnostic tests and also make for more effective management. Another important contributor to effective management of this form of gastrointestinal disorder is the adequate understanding of the mechanism by which implicated drugs induce them. In the present study, losartan, an important antihypertensive implicated in diarrhoea, constipation and abdominal cramps (mechanisms of which are yet to be well understood) was investigated. The study was done to examine the action of losartan on gastrointestinal smooth muscles. Rats’ caecum and duodenum tissues (4-5 cm) were excised, suspended in tissue baths with aerated physiological solution maintained at 35 to 37oC and connected to a computerized data acquisition system via isometric force transducers. Summarily, this method involves the use of an isolated tissue experimental set up to study the effect of drugs on the motility of gastrointestinal smooth muscles. It allows us to measure both the direct effect of such drugs as well as the influence of the drugs on homeostatic endogenous pathways such as the parasympathetic and sympathetic nervous system, largely due to the exogenous availability of the neurotransmitters of these systems.
Abstract: Ouabain (Oua)-induced hypertension in rodents provides a model to study cardiovascular changes associated with human hypertension. We examined vascular function in rats after a long-term treatment with Oua. Systolic blood pressure was measured by tail-cuff plethysmography in male Sprague-Dawley rats treated with Oua (≈ 25 µg/d) or placebo for 8 weeks. Blood pressure increased in Oua-treated animals, reaching 30% above baseline systolic blood pressure after 7 weeks. At the end of treatment, vascular responses were studied in mesenteric resistance arteries (MRAs) by wire myography. Contraction to potassium chloride in intact and denuded arteries showed greater sensitivity in Oua-treated animals. Contraction to phenylephrine and relaxation to acetylcholine were similar between groups with a lower response to sodium nitroprusside in Oua-treated arteries. Sensitivity to endothelin-1 was higher in Oua-treated arteries. Na⁺-K⁺ ATPase activity was decreased in MRAs from Oua-treated animals, whereas protein expression of the Na⁺-K⁺ ATPase α₂ isoform was increased in heart and unchanged in mesenteric artery. Preincubation with indomethacin (10⁻⁵ M) or Nω-nitro-L-arginine methyl ester (10⁻⁴ M) abolished the differences in potassium chloride response and Na⁺-K⁺ ATPase activity. Changes in MRAs are consistent with enhanced vascular smooth muscle cell reactivity, a contributor to the increased vascular tone observed in this model of hypertension.
Pub.: 26 Apr '13, Pinned: 27 Nov '17
Join Sparrho today to stay on top of science
Discover, organise and share research that matters to you