van Uum S H M, Hermus A R M M, Sweep C G J, Walker B R, Ross H A, de Leeuw P W, Lenders J W M
Department of Medicine, University Medical Center Nijmegen, Nijmegen, The Netherlands.
Eur J Clin Invest. 2002 Dec;32(12):874-81. doi: 10.1046/j.1365-2362.2002.01097.x.
Vascular tone is increased in primary hypertension, and glucocorticoids affect vascular tone. Local cortisol availability is modulated by activity of 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD). As this activity may be decreased in patients with primary hypertension, vascular sensitivity to cortisol may be increased in these patients. We studied the acute effect of cortisol on forearm vascular resistance (FVR) by infusing cortisol directly into the brachial artery, both with and without inhibition of 11 beta-HSD, in normotensive and hypertensive subjects.
Twenty normotensive volunteers and 20 patients with primary hypertension participated in the study. After a 10-min infusion of vehicle (glucose 5%), cortisol was infused into the brachial artery in three stepwise increasing doses (3.5, 10.5 and 35 microg per 100 mL of forearm volume), each for 10 min. Next, the participants received placebo or 500 mg glycyrrhetinic acid (GA) orally, and 150 min later the same infusion schedule was repeated. Forearm vascular resistance was measured during the last 5 min of the infused vehicle and of each dose. Arterial and forearm venous plasma samples for measurement of cortisol and cortisone were taken at the end of the infusions of glucose 5% and the highest cortisol dose.
In both normotensive and hypertensive subjects, neither the infusion of cortisol nor the administration of GA changed FVR. Also 2 h after the cortisol infusion there remained no change in FVR in both the normotensive and hypertensive groups who received placebo. Following the infusion of the highest cortisol dose, total plasma cortisone levels in the venous plasma were decreased compared with levels in the arterial plasma (36 +/- 3 and 49 +/- 4 nmol L-1, respectively, P < 0.05). The protein-bound venous cortisone was 37.1 +/- 4.8 nmol L-1 during the vehicle compared with 23.9 +/- 3.7 nmol L-1 during the cortisol infusion (P < 0.01), whereas the free cortisone level was not altered by the cortisol infusion.
In both normotensive and hypertensive subjects, high-dose cortisol infusion both with and without 11 beta-HSD inhibition did not change FVR either immediately or after 2 h. We could not demonstrate in vivo 11 beta-HSD activity in the forearm vascular tissues. When binding of cortisone to CBG is changed, e.g. during cortisol infusion, arterio-venous changes in cortisone cannot reliably be used to assess (alterations in) local 11 beta-HSD activity.
原发性高血压患者血管张力增加，糖皮质激素可影响血管张力。局部皮质醇的可利用性受11β-羟类固醇脱氢酶（11β-HSD）活性调节。由于原发性高血压患者的这种活性可能降低，这些患者对皮质醇的血管敏感性可能增加。我们通过直接向肱动脉输注皮质醇，在有或无11β-HSD抑制的情况下，研究了皮质醇对正常血压和高血压受试者前臂血管阻力（FVR）的急性影响。
20名正常血压志愿者和20名原发性高血压患者参与了本研究。在输注10分钟载体（5%葡萄糖）后，分三步以递增剂量（每100 mL前臂体积3.5、10.5和35 μg）向肱动脉输注皮质醇，每次输注10分钟。接下来，参与者口服安慰剂或500 mg甘草次酸（GA），150分钟后重复相同的输注方案。在输注载体和各剂量的最后5分钟测量前臂血管阻力。在输注5%葡萄糖和最高皮质醇剂量结束时，采集动脉和前臂静脉血浆样本以测定皮质醇和可的松。
在正常血压和高血压受试者中，输注皮质醇和给予GA均未改变FVR。在接受安慰剂的正常血压和高血压组中，皮质醇输注2小时后FVR也没有变化。输注最高皮质醇剂量后，静脉血浆中总可的松水平与动脉血浆水平相比降低（分别为36±3和49±4 nmol/L，P<0.05）。与输注载体时相比，蛋白结合的静脉可的松在输注载体时为37.1±4.
