Given B D, Vita N A, Black H R, Francis C, Lasseter K, Morray R L, Mickiewicz C, Akester J, Koury K, Dzau V J
Hypertension. 1986 Jun;8(6):489-96. doi: 10.1161/01.hyp.8.6.489.
Endogenous prostaglandin E2 appears to play an important role in cardiovascular homeostasis. When administered exogenously, it is a potent vasodilator, but the requirement for intravenous administration and its short duration of action have limited studies to its acute effects. A novel prostaglandin E2 analogue, CL 115347, can be administered transdermally on a long-term basis. The cardiovascular responses to the chronic administration of CL 115347 were studied in a double-blind, placebo-controlled trial in 26 subjects with essential hypertension (16 given drug, 10 placebo) maintained on a 100-mEq sodium diet. Administration of CL 115347 produced a fall in diastolic blood pressure of 7.8 +/- 1.3 mm Hg, compared with a 2.3 +/- 1.7 mm Hg fall in controls (p = 0.02), with no change in heart rate. The direct vascular effect of the drug was confirmed by attenuation of the vasoconstrictor response to angiotensin II infusion (13.4 +/- 3.1 vs 21 +/- 2 mm Hg at 3.0 ng/kg/min; p less than 0.05). However, the chronic blood pressure effect of CL 115347 was modest. Subjects receiving active drug showed significant compensatory increases in plasma renin, aldosterone, and norepinephrine levels accompanied by sodium retention and kaliuresis. In summary, chronic administration of this prostaglandin E2 analogue resulted in a modest decrease in blood pressure and antagonism of angiotensin II-mediated vasoconstriction. However, its effects were largely offset by compensatory increases in vasoconstrictor hormones and sodium retention.
内源性前列腺素E2似乎在心血管稳态中发挥重要作用。当外源性给药时，它是一种强效血管扩张剂，但静脉给药的要求及其作用持续时间短限制了对其急性效应的研究。一种新型前列腺素E2类似物CL 115347可以长期经皮给药。在一项双盲、安慰剂对照试验中，对26名原发性高血压患者（16名给予药物，10名给予安慰剂）进行了研究，这些患者维持100 mEq钠饮食，以观察CL 115347长期给药后的心血管反应。与对照组舒张压下降2.3±1.7 mmHg相比，给予CL 115347后舒张压下降7.8±1.3 mmHg（p = 0.02），心率无变化。通过减弱对血管紧张素II输注的血管收缩反应证实了该药物的直接血管作用（在3.0 ng/kg/min时为13.4±3.1 vs 21±2 mmHg；p＜0.05）。然而，CL 115347对血压的慢性影响较小。接受活性药物的受试者血浆肾素、醛固酮和去甲肾上腺素水平显著代偿性升高，伴有钠潴留和尿钾增多。总之，长期给予这种前列腺素E2类似物导致血压适度下降，并拮抗血管紧张素II介导的血管收缩。然而，其作用在很大程度上被血管收缩激素的代偿性增加和钠潴留所抵消。
