1. We measured forearm blood flow during brachial artery infusions of vasoconstrictors (angiotensin II and noradrenaline) and vasodilators (sodium nitroprusside and carbachol) in 16 healthy control subjects and in 18 patients with uncomplicated insulin-dependent diabetes mellitus. Erythrocyte Na+/Li+ countertransport and platelet Na+/H+ antiport activities were also measured. 2. The mean basal forearm vascular resistance was 22% lower in diabetic patients than in control subjects. The effects of each infusion on forearm vascular resistance were similar in diabetic patients and control subjects. 3. Erythrocyte Na+/Li+ countertransport activities were similar in diabetic patients and control subjects. Platelet Na+/H+ exchange (Vmax) was approximately 40% greater in diabetic patients than in control subjects, whereas the Km for Na+ was similar. 4. In diabetic patients, but not in control subjects, the responses to sodium nitroprusside and carbachol correlated inversely with Na+/Li+ countertransport in erythrocytes (rs = -0.76, P less than 0.001, and rs = -0.66, P less than 0.005, respectively), but not with Na+/H+ exchange in platelets.
B1-and B2-receptors. 4 Kinin-induced ftlaxation was reversibly antagonized by ibuprofen (a cyclo-oxygenase inhibitor) and by 5-(N,N-hexamethylene)amiloride (an inhibitor of Na+/H+ exchange). Ibuprofen caused a parallel shift to the right of a semi-logarithmic plot of the agonist concentration-effect relationship, whereas the amiloride analogue depressed the maximum response and reduced the slope. 5 We conclude that bradykinin and des Arg10-kallidin relax rabbit coeliac artery by combining with B1-receptors. The response is mediated by a cyclo-oxygenase product and may be influenced by cellular Na+/H+ exchange.
Short-term effects of ridogrel, a combined thromboxane synthase inhibitor and receptor antagonist, were investigated in 16 patients with uncomplicated essential hypertension. After a 2-week placebo period without antihypertensive medication, patients were admitted to the hospital overnight on two occasions 3 weeks apart On each occasion, they received two doses of either placebo or ridogrel (300 rag) 12 hours apart according to a double-blind crossover protocol. Renal and systemic thromboxane A 2 and prostacyclin biosynthesis were investigated by measuring urinary excretion of thromboxane B 2 , 6-oxoprostaglandin F lo , and their respective 2,3-dinor metabolites using gas chromatography/mass spectrometry. Responses of platelets to a thromboxane A 2 mimetic and to adenosine diphosphate were studied turbidometrically. Blood pressure was measured automatically at 20-minute intervals. Ridogrel reduced excretion of 2,3-dinor-thromboxane B 2 and thromboxane Bj compared with placebo (21 ±6 versus 279±28 and 14±4 versus 39±9 ng/g creatinine, respectively, P<.0001 and P<.05). Excretion of 2,3-dinor-6-oxoprostaglandin F 1(r and 6-oxoprostaglandin F, o was increased by ridogrel compared with placebo (184±20 versus 146±11 and 86±9 versus 58±6 ng/g creatinine, respectively; P<.0S). Ridogrel selectively antagonized platelet aggregation to the thromboxane mimetic (P<.0001). Blood pressure did not differ significantly between ridogrel and placebo treatment periods. Thus, in patients with essential hypertension, acute administration of ridogrel reduces renal and extrarenal thromboxane A 2 biosynthesis, increases renal and extrarenal prostacyclin biosynthesis, inhibits thromboxane receptor-activated platelet aggregation, but has no effect on systemic arterial pressure. (Hypertension 1993^22:197-203)
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.