Chillon J M, Baumbach G L
Cardiovascular Research Group, Faculty of Pharmacy, University of Nancy, Nancy, France.
Hypertension. 2001 Jun;37(6):1388-93. doi: 10.1161/01.hyp.37.6.1388.
We examined the effects of the angiotensin-converting enzyme inhibitor perindopril and the beta-blocker propranolol on dilator responses of cerebral arterioles in chronic hypertension. Dilator responses to acute hypotension were examined in untreated Wistar-Kyoto rats (WKY) and stroke-prone spontaneously hypertensive rats (SHRSP) that were untreated or treated for 3 months with a low (0.3 mg. kg(-1). day(-1)) or a high (2 mg. kg(-1). day(-1)) dose of perindopril or a dose of propranolol (250 mg. kg(-1). day(-1)) alone or in combination with the low dose of perindopril. Pressure (servo-null) and diameter were measured in cerebral arterioles during acute reductions in arterial pressure both before and during maximal dilatation (EDTA). The high dose of perindopril or the combination of propranolol and perindopril normalized cerebral arteriolar pressure (52+/-2 [mean+/-SEM], 49+/-2 mm Hg versus 50+/-2 mm Hg in WKY and 96+/-3 mm Hg in untreated SHRSP; P<0.05). In contrast, the low dose of perindopril or propranolol alone did not normalize arteriolar pressure (74+/-2 mm Hg and 58+/-3 mm Hg). Both the low and high doses of perindopril improved autoregulatory dilatation, maximal dilatation, and dilator reserve of cerebral arterioles in SHRSP, with the low dose of perindopril being almost as effective as the high dose of perindopril. Propranolol alone did not significantly improve dilator function of cerebral arterioles. Furthermore, dilator function of cerebral arterioles was not further improved by the addition of propranolol to the low dose of perindopril. These findings suggest that angiotensin-converting enzyme inhibitors, such as perindopril, may be more effective than propranolol in attenuating the impairment of cerebral autoregulatory vasodilatation, maximal dilatation, and dilator reserve during treatment of chronic hypertension.
我们研究了血管紧张素转换酶抑制剂培哚普利和β受体阻滞剂普萘洛尔对慢性高血压患者脑动脉扩张反应的影响。在未经治疗的Wistar-Kyoto大鼠(WKY)和易中风自发性高血压大鼠(SHRSP)中,检测了对急性低血压的扩张反应,这些大鼠未经治疗或用低剂量(0.3mg·kg⁻¹·d⁻¹)或高剂量(2mg·kg⁻¹·d⁻¹)的培哚普利或剂量为250mg·kg⁻¹·d⁻¹的普萘洛尔单独治疗或与低剂量培哚普利联合治疗3个月。在急性动脉压降低期间,在最大扩张(EDTA)之前和期间,测量脑动脉的压力(伺服零位)和直径。高剂量的培哚普利或普萘洛尔与培哚普利的组合使脑动脉压正常化(52±2[平均值±标准误],49±2mmHg,而WKY中为50±2mmHg,未经治疗的SHRSP中为96±3mmHg;P<0.05)。相比之下,低剂量的培哚普利或单独的普萘洛尔并未使动脉压正常化(74±2mmHg和58±3mmHg)。低剂量和高剂量的培哚普利均改善了SHRSP脑动脉的自动调节扩张、最大扩张和扩张储备,低剂量的培哚普利几乎与高剂量的培哚普利一样有效。单独使用普萘洛尔并未显著改善脑动脉的扩张功能。此外,在低剂量培哚普利中添加普萘洛尔并未进一步改善脑动脉的扩张功能。这些发现表明,血管紧张素转换酶抑制剂,如培哚普利,在减轻慢性高血压治疗期间脑自动调节血管舒张、最大扩张和扩张储备的损害方面可能比普萘洛尔更有效。