We examined a relation between cyclic guanosine monophosphate (cGMP) production in thoracic aorta, as an indicator probably reflecting the vascular response, and the vascular as well as plasma levels of nicorandil administered orally to rats. Nicorandil (3 mg/kg) given orally was rapidly absorbed, reaching the maximal plasma (approximately 2,600 ng/ml) and vascular concentrations (approximately 176 ng/g) at 15 min after the dosing and thereafter decreased rapidly. Even 2 h after the dosing, the level of the vascular cGMP formation in vivo remained significantly higher (approximately 1,000 fmol/mg increase from the control level) in the nicorandil-treated group, compared with the vehicle-treated one, and was enough to develop pronounced muscle relaxation in in vitro aortic preparations. However, it seems that the vascular cGMP increase in vivo was not always correlated to the plasma concentration of nicorandil, because the plasma concentration (approximately 750 ng/ml corresponding to 3.5 microM) at 2 h after the dosing, caused only relatively low cGMP production (300-400 fmol/mg increase from the control level), when tested in in vitro aortic preparations. Our study may indicate, therefore, that the vascular cGMP elevation in vivo is due to the content of nicorandil effectively remaining at its vascular targets of action as well as the plasma nicorandil concentration.
Dermatan sulfate excreted in normal human urine was isolated and characterized by TLC and cellulose acetate strip electrophoresis after cetylpyridinium chloride precipitation and pronase digestion. In these separation methods, dermatan sulfate and chondroitin sulfate were extracted and then monitored by sensitive HPLC methods with post column fluorometric derivatization coupled with chondroitinase ABC, ACII and B digestion. From the results, we demonstrated that human urinary dermatan sulfate contains iduronic acid as its major uronic acid (80-90% of total uronic acid), and is composed mainly of repeated mono-sulfated disaccharide units [Di-4S (structure shown in Fig. 1), 89%] and small numbers of di-sulfated disaccharide units (Di-diSB, 7% and Di-diSE, 1%).
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