Benetos A, Cambien F, Gautier S, Ricard S, Safar M, Laurent S, Lacolley P, Poirier O, Topouchian J, Asmar R
Institut National de la Santé et de la Recherche Médicale (INSERM) U337, Broussais Hospital, Paris, France.
Hypertension. 1996 Dec;28(6):1081-4. doi: 10.1161/01.hyp.28.6.1081.
Angiotensin-converting enzyme inhibitors improve arterial stiffness independently of blood pressure reduction. Since we have recently shown that in hypertensive individuals the A1166C polymorphism of the angiotensin II type 1 receptor (AT1-R) is an independent determinant of aortic stiffness, we designed the present study to assess the influence of this polymorphism on the changes of aortic stiffness after chronic treatment with the angiotensin-converting enzyme inhibitor perindopril and the calcium channel blocker nitrendipine. Forty perindopril- and 42 nitrendipine-treated hypertensive individuals were studied. We evaluated aortic stiffness by measuring the carotid-femoral pulse wave velocity. Carriers of the AT1-RC allele showed higher baseline values of pulse wave velocity than AA homozygotes (P < .05). In the perindopril group, a threefold greater reduction in pulse wave velocity was observed in carriers of the C allele than in AA homozygotes (-2.85 +/- 0.62 versus -0.94 +/- 0.32 m/s, respectively; P < .001), whereas in the nitrendipine group, pulse wave velocity decreased only in AA homozygotes and not in AT1-R C carriers (-1.38 +/- 0.35 versus +0.04 +/- 0.60 m/s, respectively; P < .01). These results indicate that according to the AT1-R A1166C genotype, an angiotensin-converting enzyme inhibitor and a calcium channel blocker affect pulse wave velocity in opposite ways. Since some evidence shows that increased pulse wave velocity may enhance cardiovascular risk, it might be useful for physicians to consider the AT1-R genotype when prescribing an angiotensin-converting enzyme inhibitor or calcium channel blocker to a hypertensive individual.
血管紧张素转换酶抑制剂可独立于血压降低改善动脉僵硬度。由于我们最近发现,在高血压个体中,血管紧张素II 1型受体(AT1-R)的A1166C多态性是主动脉僵硬度的独立决定因素,我们设计了本研究,以评估这种多态性对血管紧张素转换酶抑制剂培哚普利和钙通道阻滞剂尼群地平长期治疗后主动脉僵硬度变化的影响。对40例接受培哚普利治疗和42例接受尼群地平治疗的高血压个体进行了研究。我们通过测量颈股脉搏波速度来评估主动脉僵硬度。AT1-R C等位基因携带者的脉搏波速度基线值高于AA纯合子(P <.05)。在培哚普利组中,C等位基因携带者的脉搏波速度降低幅度比AA纯合子大三倍(分别为-2.85 +/- 0.62与-0.94 +/- 0.32 m/s;P <.001),而在尼群地平组中,脉搏波速度仅在AA纯合子中降低,而在AT1-R C携带者中未降低(分别为-1.38 +/- 0.35与+0.04 +/- 0.60 m/s;P <.01)。这些结果表明,根据AT1-R A1166C基因型,血管紧张素转换酶抑制剂和钙通道阻滞剂以相反的方式影响脉搏波速度。由于一些证据表明脉搏波速度增加可能会增加心血管风险,因此医生在给高血压个体开血管紧张素转换酶抑制剂或钙通道阻滞剂时考虑AT1-R基因型可能是有用的。