Cinquegrani M P, Liang C S
Department of Medicine (Cardiology Unit), University of Rochester Medical Center, New York 14642.
Clin Exp Hypertens A. 1988;10(3):411-31. doi: 10.3109/10641968809033901.
To determine the potential role of prostaglandins in mediating the hypotensive action of the new antihypertensive agent pinacidil, we measured the blood pressure, regional blood flow and neurohumoral responses to pinacidil in thirteen hypertensive patients randomly assigned to receive pretreatment with either indomethacin (75 mg) or placebo. After baseline measurements had been obtained, each patient received an oral dose of pinacidil to which he had previously demonstrated a therapeutic response. The doses of pinacidil administered between the two groups did not differ. Serial measurements of blood pressure and heart rate over two hours revealed no attenuation of the hypotensive effect of pinacidil in the indomethacin-pretreated patients (-12.7 +/- 4.1 mm Hg) compared to the placebo group (-9.3 +/- 3.2 mm Hg). While significant vasodilation was not observed in the forearm, renal vasodilation occurred and was not different between the two groups. Pinacidil had no effect on glomerular filtration rate. Neither did pinacidil significantly increase plasma catecholamines or renin activity. The results indicate that prostaglandins probably do not play a major role in the vasodilator action of pinacidil, and that therapeutic doses of the drug have a differential effect on regional blood flows that result in hypotension, but not significant neurohumoral stimulation, in patients with mild to moderate hypertension.
为了确定前列腺素在介导新型抗高血压药物吡那地尔的降压作用中所起的潜在作用，我们对13例高血压患者进行了研究，这些患者被随机分配接受吲哚美辛（75毫克）或安慰剂预处理，我们测量了他们对吡那地尔的血压、局部血流和神经体液反应。在获得基线测量值后，每位患者口服一剂吡那地尔，此前他们已证明对该药有治疗反应。两组患者服用的吡那地尔剂量没有差异。两小时内对血压和心率的连续测量显示，与安慰剂组（-9.3±3.2毫米汞柱）相比，吲哚美辛预处理患者中吡那地尔的降压效果没有减弱（-12.7±4.1毫米汞柱）。虽然在前臂未观察到明显的血管舒张，但出现了肾血管舒张，且两组之间没有差异。吡那地尔对肾小球滤过率没有影响。吡那地尔也没有显著增加血浆儿茶酚胺或肾素活性。结果表明，前列腺素可能在吡那地尔的血管舒张作用中不发挥主要作用，并且该药物的治疗剂量对局部血流有不同的影响，从而导致轻度至中度高血压患者出现低血压，但不会引起明显的神经体液刺激。
