To assess the contribution of sympathetic outflow to blood pressure in patients with essential hypertension, we measured blood pressure and plasma norepinephrine responses to clonidine, an antihypertensive agent that decreases central sympathetic outflow, in 44 patients and in 41 normotensive control subjects of similar age. Among the hypertensive patients, the resting level of plasma norepinephrine was significantly related to the decrease in mean arterial pressure 3 hours after a single oral dose of clonidine 300 micrograms (r = 0.62, p less than 0.001). The magnitude of the depressor response in the patients also was correlated significantly with the decrease in plasma norepinephrine after clonidine (r = 0.60, p less than 0.001). These results suggest that increased sympathetic outflow plays a pathophysiologic role in some patients with essential hypertension.
Four subjects were studied by continuous intraduodenal sampling to establish the existence and determine the extent of enterohepatic recirculation of sulindac and its sulfide and sulfone metabolites. Sulindac, 200 mg by mouth, was given every 12 hr for 7 days. After the last dose was given intraduodenally, constant duodenal infusion of a nutrient mixture and sampling of duodenal contents were performed through a triple-lumen intraduodenal tube for 12 hr. Calculation of nonabsorbed drug in the samples and quantitation of drug and metabolite levels in the biliary secretions were made possible by nonabsorbable markers in the drug solution and in the infusate. Interindividual variations in the absolute values for each of the chemical species were over a 200% range, but for each subject relative clearances were in a remarkably constant ratio, averaging 1:12:12 for sulfide:sulindac:sulfone. Total biliary excretions of the prodrug (sulindac) and active pharmacophore (sulfide) calculated from these biliary clearances and historic mean plasma AUCs were 136% and 22% of dose. Thus, there is a correlation between data in man and those in five other species and the data established that, after sulindac, the contribution of enterohepatic circulation to conservation of the active pharmacophore is achieved predominantly at the level of inactive prodrug.
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.