ABSTRACT
Epoxyeicosatrienoic acids (EETs) are endogenous ligands that undergo hydrolysis by soluble epoxide hydrolase (sEH). The responses of 11, 12-EET in comparison with other vasodilator agonists including carbachol and sodium nitroprusside (SNP) were investigated. The effect of 1-cyclohexyl-3-dodecyl urea (CDU), a sEH, was tested on the vasodilator effect induced by 11, 12-EET in the perfused mesenteric beds isolated from normo-glycaemic and type-1 STZ-diabetic rats. In the perfused mesenteric beds of control and diabetic animals, 11, 12-EET produced vasodilation in a dose-dependent manner. The vasodilator response induced by 11, 12-EET was significantly decreased in tissues obtained from diabetic animals, but this was significantly corrected through inhibition of sEH. The effects of nitric oxide synthase inhibitor, cyclo-oxygenase inhibitor, specific potassium channel inhibitors, soluble guanylyl cyclase inhibitor and transient receptor potential channel V4 inhibitor, on vasodilator response to 11, 12-EET were investigated. In tissues isolated from control animals, vasodilator responses to 11, 12-EET were not inhibited by acute incubation with l-NAME, l-NAME with indomethacin, glibenclamide, iberiotoxin, charybdotoxin, apamin or ODQ. Incubation with the transient receptor potential channel V4 inhibitor ruthenium red caused significantly reduced vasodilator responses induced by 11, 12-EET. In conclusion, results from this study indicate that 11, 12-EET has a vasodilator effect in the perfused mesenteric bed, partly through activation of vanilloid receptor. A strategy to elevate the levels of EETs may have a significant impact in correcting microvascular abnormality associated with diabetes.
Subject(s)
8,11,14-Eicosatrienoic Acid/analogs & derivatives , Splanchnic Circulation/drug effects , Vasodilator Agents/pharmacology , 8,11,14-Eicosatrienoic Acid/pharmacology , Animals , Cyclooxygenase Inhibitors/pharmacology , Diabetes Mellitus, Experimental/physiopathology , Dose-Response Relationship, Drug , Drug Interactions , Enzyme Inhibitors/pharmacology , Guanylate Cyclase/antagonists & inhibitors , Male , Nitric Oxide Synthase/antagonists & inhibitors , Perfusion , Potassium Channel Blockers/pharmacology , Rats , Rats, Sprague-Dawley , Transient Receptor Potential Channels/antagonists & inhibitorsABSTRACT
OBJECTIVE: The objectives of this study were to evaluate the perceptions, expectations and experience of physicians with hospital-based pharmacists in Kuwait. MATERIALS AND METHODS: A piloted self-administered questionnaire was hand delivered to 200 physicians practicing in four government hospitals in Kuwait. Main sections of the questionnaire comprised a series of statements pertaining to physicians' perceptions, expectations and experiences with pharmacists. RESULTS: One hundred and twenty (60%) questionnaires were returned. At least 57% of physicians in Kuwait appear comfortable with pharmacists carrying out patient-directed roles. In addition, they appeared to have high expectations of pharmacists, with 79% of them regarding pharmacists as knowledgeable drug therapy experts. Less than 60% considered pharmacists as applying their drug knowledge in practice and only 29% agreed that pharmacists routinely counselled their patients. There was no correlation between physician variables such as number of years since graduation from medical school, age, area of practice and their perceptions of pharmacists. CONCLUSION: Physicians in Kuwait appear comfortable with pharmacists providing a broad range of services but appear somewhat less comfortable with pharmacists' provision of direct patient care. Physicians considered pharmacists knowledgeable drug therapy experts, but regarded them as not routinely providing a broad range of higher-level pharmacy services.
