Fridman K, Andersson O K, Wysocki M, Friberg P, Sunzel M
Department of Clinical Physiology, Sahlgrenska University Hospital, Gothenborg, Sweden.
Eur J Clin Pharmacol. 1998 Sep;54(7):497-501. doi: 10.1007/s002280050503.
This study was performed to assess the acute effects of the new angiotensin II antagonist, candesartan cilexetil, on systemic and renal haemodynamics in patients with sustained essential hypertension [diastolic blood pressure (DBP) 95-114 mmHg].
After 4 weeks of placebo treatment, systemic and renal haemodynamics were investigated in 17 patients with a mean age of 62 years and a mean systolic and diastolic blood pressure of 170/98 mmHg, just before (baseline) and for 4 h after administration of a single oral dose of candesartan cilexetil, 16 mg. Plasma concentrations of candesartan (the active compound formed from the pro-drug candesartan cilexetil), angiotensin II (Ang II), as well as plasma renin activity (PRA), were measured before and after dosing.
At 2, 3 h and 4 h after dosing with candesartan cilexetil, systolic blood pressure (SBP) and DBP, as well as mean arterial pressure (MAP), were significantly lower than at baseline. The mean reduction in MAP 4 h after dosing was 8.8 mmHg (-6.5%). This effect was due to a fall in total peripheral resistance (TPR), while heart rate (HR), stroke volume (SV) and cardiac output (CO) were virtually unchanged. After 4 h there was a marked reduction in renal vascular resistance (RVR) of 0.0273 mmHg x ml(-1) x min (-16%), resulting in an increased renal plasma flow of 64.9 ml x min(-1) (14%). The glomerular filtration rate was increased by 7.75 ml x min(-1) (8%), and the filtration fraction (FF) was not significantly changed. There was no apparent relationship between the changes observed in systemic and renal haemodynamic variables and plasma concentrations of candesartan. Plasma renin activity increased over the study period, but in general the patients had low PRA. Changes in plasma concentrations of angiotensin II were inconsistent between patients.
A single oral tablet of candesartan cilexetil, 16 mg, induced systemic and renal arterial vasodilatation and blood pressure reduction, without compromising renal perfusion or filtration or affecting cardiac performance. Plasma renin activity which was low in general, increased over the study period, but changes in plasma concentrations of angiotensin II were inconsistent.
本研究旨在评估新型血管紧张素II拮抗剂坎地沙坦酯对持续性原发性高血压患者（舒张压95 - 114mmHg）全身及肾脏血流动力学的急性影响。
在17名平均年龄62岁、平均收缩压和舒张压为170/98mmHg的患者中，经过4周安慰剂治疗后，在单次口服16mg坎地沙坦酯前（基线）及给药后4小时，对其全身及肾脏血流动力学进行研究。给药前后测量坎地沙坦（前体药物坎地沙坦酯转化形成的活性化合物）、血管紧张素II（Ang II）的血浆浓度以及血浆肾素活性（PRA）。
服用坎地沙坦酯后2、3和4小时，收缩压（SBP）、舒张压（DBP）以及平均动脉压（MAP）均显著低于基线水平。给药4小时后MAP平均降低8.8mmHg（-6.5%）。此效应归因于总外周阻力（TPR）下降，而心率（HR）、每搏输出量（SV）和心输出量（CO）基本未变。4小时后肾血管阻力（RVR）显著降低0.0273mmHg×ml⁻¹×min（-16%），导致肾血浆流量增加64.9ml×min⁻¹（14%）。肾小球滤过率增加7.75ml×min⁻¹（8%），滤过分数（FF）无显著变化。全身及肾脏血流动力学变量的变化与坎地沙坦血浆浓度之间无明显关系。研究期间血浆肾素活性升高，但总体上患者PRA较低。患者间血管紧张素II血浆浓度变化不一致。
单次口服16mg坎地沙坦酯可引起全身及肾动脉血管舒张和血压降低，而不影响肾灌注或滤过，也不影响心脏功能。总体较低的血浆肾素活性在研究期间升高，但血管紧张素II血浆浓度变化不一致。
