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The effect of both administration and withdrawal of doxazosin on patients with essential hypertension was evaluated by twenty-four-hour ambulatory blood pressure (BP) monitoring. Six hypertensive men were treated with doxazosin starting at 1 mg/day, and the dosage was titrated at weekly intervals up to a maximum of 8 mg/day. The twenty-four-hour BP profile was monitored noninvasively before treatment, in the fourth week of treatment, and on days 2 and 7 after the discontinuation of doxazosin. The average twenty-four-hour systolic and diastolic BPs (SBP and DBP) were lowered by doxazosin treatment and returned to the pretreatment levels within two days of doxazosin withdrawal. Doxazosin treatment produced a significant decrease in the daytime SBP and DBP but not in the nighttime BP values. The daytime BP decrease was no longer detected on days 2 and 7 after drug withdrawal. The twenty-four-hour pulse rate was not influenced by either doxazosin administration or discontinuation. The plasma norepinephrine concentration and plasma renin activity were increased by doxazosin treatment and were decreased by drug withdrawal. There was no rebound hypertension following doxazosin withdrawal. Thus, the present study using twenty-four-hour BP monitoring showed that doxazosin treatment reduced the daytime BP in patients with essential hypertension and that this reduction was abolished within two days after doxazosin discontinuation.

Adrenomedullin(AM)is a vasodilatory hormone secreted mainly by the vascular wall, and its expression is remarkably enhanced after stroke. Several studies have shown that AM inhibits ischemic injury in the brain. The present study investigates the effects of AM on nitric oxide(NO)production during forebrain ischemia and reperfusion. Halothane anesthesia was administered to AM-knockout(AM )and control(C57 BL 6J)mice and then NO production was continuously monitored in the left striatum by in vivo microdialysis. A laser Doppler probe was fixed on the right scalp to measure relative cerebral blood flow(rCBF)continuously. Blood pressure(BP), blood gases and body temperature were monitored and physiologically maintained. After equilibrium for 2 hours, fractions were collected every 10 minutes. Forebrain cerebral ischemia was produced by occluding both common carotid arteries. After 10 minutes, the loops around both common carotid arteries were released. Levels of nitrite and nitrate in dialysates were determined using the Griess reaction. At 6 hours after forebrain cerebral ischemia, the degrees of the ischemic damage in hippocampal CA1 neurons were investigated. Knockout of the AM gene did not affect BP and rCBF. Levels of total NO(nitrite+nitrate) were lower in AM-knockout mice at baseline, during ischemia and after reperfusion. The survival cell rate of hippocampal CA1 neurons in AM-knockout mice was lower than that of control mice. These data suggest that AM exert protective effects by activating NO synthase in the brain during ischemia and reperfusion. (Cerebral Blood Flow and Metabolism 21:1―6,2010)

To elucidate the role of renal maltase in the metabolism of circulating maltose, glucose production from maltose was investigated in perfused kidney of normal and streptozotocin (STZ) diabetic rats. The kidney was perfused with 150 mg/dl maltose for 30 min and perfusate maltose and glucose were measured. Perfusate glucose concentration in the kidney of control rats gradually increased during perfusion. That in the kidney of diabetic rats was significantly lower than that in controls. Perfusate maltose concentration in the kidney of diabetic rats was significantly higher than that in controls. These results suggest that circulating maltose may enter kidney cells and subsequently metabolized to glucose, and that maltose uptake and glucose production were decreased in the kidney of STZ diabetic rats.